Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yoshinao Oda Last modified date:2020.10.01

Professor / Department of Anatomic Pathology / Department of Basic Medicine / Faculty of Medical Sciences


Papers
1. Makoto Hirata, Naofumi Asano, Kotoe Katayama, Akihiko Yoshida, Yusuke Tsuda, Masaya Sekimizu, Sachiyo Mitani, Eisuke Kobayashi, Motokiyo Komiyama, Hiroyuki Fujimoto, Takahiro Goto, Yukihide Iwamoto, Norifumi Naka, Shintaro Iwata, Yoshihiro Nishida, Toru Hiruma, Hiroaki Hiraga, Hirotaka Kawano, Toru Motoi, Yoshinao Oda, Daisuke Matsubara, Masashi Fujita, Tatsuhiro Shibata, Hidewaki Nakagawa, Robert Nakayama, Tadashi Kondo, Seiya Imoto, Satoru Miyano, Akira Kawai, Rui Yamaguchi, Hitoshi Ichikawa, Koichi Matsuda, Integrated exome and RNA sequencing of dedifferentiated liposarcoma , Nature communications, 10.1038/s41467-020-14680-8, 11, 1, (Nature Communications, (2019), 10, 1, (5683), 10.1038/s41467-019-13286-z), 2020.12, The original version of this Article contained an error in Fig. 4, in which samples marked with blue dots were labelled with the suffix ‘WD’ instead of ‘DD’. This has now been corrected in both the PDF and HTML versions of the Article..
2. Kinoshita F, Takada K, Yamada Y, Oku Y, Kosai K, Ono Y, Tanaka K, Wakasu S, Oba T, Osoegawa A, Tagawa T, Shimokawa M, Oda Y, Mori M., Combined Evaluation of Tumor-Infiltrating CD8 + and FoxP3 + Lymphocytes Provides Accurate Prognosis in Stage IA Lung Adenocarcinoma., Ann Surg Oncol., 27(6):2102-2109, 2020.06.
3. Yukihiko Okumura, Kenichi Kohashi, Yuki Tanaka, Masaki Kato, Yoshihiko Maehara, Yoshihiro Ogawa, Yoshinao Oda, Activation of the Akt/mammalian target of rapamycin pathway in combined hepatocellular carcinoma and cholangiocarcinoma
significant correlation between p-4E-BP1 expression in cholangiocarcinoma component and prognosis, Virchows Archiv, 10.1007/s00428-019-02741-3, 2020.06, The Akt/mammalian target of rapamycin (mTOR) pathway, which plays an important role in regulating cellular functions including proliferation, motility, and invasion, is known to be activated in many cancers. Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) (cHCC-CC) has wide histological diversity characterized by relatively poor prognosis. Because of a lack of investigation into its molecular mechanisms, no effective systemic therapy is currently available for unresectable cHCC-CC tumors. Here, we retrospectively examined the clinicopathological and activation statuses of the Akt/mTOR pathway in 89 cases of cHCC-CC. Expression levels of molecular markers associated with this signaling pathway, including phosphatase and tensin homologue deleted on chromosome 10 (PTEN), phosphorylated Akt (p-Akt), p-mTOR, p-ribosomal protein S6 (p-S6RP), and p-eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (p-4E-BP1), were measured by immunohistochemical staining. In addition, such activation in different cHCC-CC morphological categories was compared by dividing cases into those with HCC (n = 86), CC (n = 78), and intermediate components (n = 60). Comparison of prognosis among these groups revealed that p-4E-BP1 immunopositivity in cHCC-CC cases containing CC a component was a significant risk factor for poorer overall survival (P = 0.041). By evaluating factors in p-4E-BP1 expression in 78 cHCC-CC cases with a CC component, only lymph node metastasis was significantly correlated with positive immunostaining for p-4E-BP1 (P = 0.0222). In conclusion, p-4E-BP1 expression, especially in cHCC-CC cases with a CC component, was a notable Akt/mTOR pathway-related factor associated with poor prognosis. Assessing histological structure and p-4E-BP1 expression in cHCC-CC may be helpful for both predicting prognosis and using molecular targeted therapy..
4. Taisuke Narazaki, Motoaki Shiratsuchi, Takamitsu Matsushima, Mariko Tsuda, Yasuhiro Tsukamoto, Hiroki Muta, Toru Masuda, Daisaku Kimura, Akiko Takamatsu, Hidetaka Yamamoto, Yoshinao Oda, Hiroaki Miyoshi, Koichi Ohshima, Yayoi Matsuda, Ryuichi Sakamoto, Yasuhiro Nakashima, Yoshihiro Ogawa, Clinico-pathological characteristics of primary adrenal lymphomas–potential efficacy of autologous stem cell transplantation, Leukemia and Lymphoma, 10.1080/10428194.2020.1725507, 2020.06.
5. Koba R, Fujita H, Nishibori M, Saeki K, Nagayoshi K, Sadakari Y, Nagai S, Sekizawa O, Nitta K, Manabe T, Ueki T, Ishida T, Oda Y, Nakamura M., Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer: In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry., Int J Cancer., 146 (9):2498-2509, 2020.05.
6. Kazuki Takada, Yasuto Yoneshima, Kentaro Tanaka, Isamu Okamoto, Mototsugu Shimokawa, Sho Wakasu, Shinkichi Takamori, Gouji Toyokawa, Taro Oba, Atsushi Osoegawa, Tetsuzo Tagawa, Yoshinao Oda, Yoichi Nakanishi, Masaki Mori, Clinical impact of skeletal muscle area in patients with non-small cell lung cancer treated with anti-PD-1 inhibitors, Journal of Cancer Research and Clinical Oncology, 10.1007/s00432-020-03146-5, 2020.05, Purpose: The aim of this study was to elucidate the clinical impact of skeletal muscle area (SMA) in patients with non-small cell lung cancer (NSCLC) treated with anti-programmed cell death-1 (PD-1) inhibitors. Methods: Univariate and multivariate analyses were performed on data of 103 patients with advanced or recurrent NSCLC treated with anti-PD-1 inhibitors. The SMA was measured at the level of the third lumbar vertebral (L3) on computed tomography images using OsiriX software (32-bit, version 5.8; OsiriX, Geneva, Switzerland). The L3 muscle index (cm2/m2) was defined as the SMA (cm2) at the L3 level divided by the height (m) squared. Results: L3 muscle index Low was an independent predictor of both progression-free (P = 0.0399) and overall survival (P = 0.0155). Moreover, the disease control rate was significantly lower in the L3 muscle index Low group (49.0% [25/51]) than in the L3 muscle index High group (73.1% [38/52]; P = 0.0117). However, there was no significant difference between the response rates of the L3 muscle index Low group (21.6% [11/51]) and L3 muscle index High group (32.7% [17/52]; P = 0.2031). Conclusions: L3 muscle index Low is an independent predictor of worse outcomes in NSCLC patients treated with anti-PD-1 inhibitors..
7. Kanako Kurata, Makoto Kubo, Masaya Kai, Hitomi Mori, Hitomi Kawaji, Kazuhisa Kaneshiro, Mai Yamada, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Masayuki Okido, Yoshinao Oda, Masafumi Nakamura, Microsatellite instability in Japanese female patients with triple-negative breast cancer, Breast Cancer, 10.1007/s12282-019-01043-5, 2020.05, Background: It is important to identify biomarkers for triple-negative breast cancers (TNBCs). Recently, pembrolizumab, an immune checkpoint inhibitor (ICI) for programmed cell death 1 (PD-1), was approved as a treatment strategy for unresectable or metastatic tumor with high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency, such as malignant melanoma, non-small cell lung cancer, renal cell cancer and urothelial cancer. In addition, results from clinical trials suggested that ICI was a promising treatment for TNBCs with accumulated mutations. However, the frequency of MSI in Japanese TNBCs still remains unclear. We aimed to analyze the presence of MSI-H in TNBCs as a biomarker for ICI therapy. Methods: In this study, we retrospectively evaluated the MSI of 228 TNBCs using an innovative method, MSI Analysis System Version 1.2 (Promega), consisting of 5 microsatellite markers: BAT-26, NR-21, BAT-25, MONO-27 and NR-24 without a normal tissue control. Results: Among 228 tumors, 222 (97.4%) were microsatellite stable, 4 (1.7%) low-frequency MSI and 2 (0.9%) MSI-H, respectively. Two MSI-H tumors were potentially aggressive pathologically as indicated by nuclear grade 3 and high Ki-67 (> 30%), and were classified as basal-like and non-BRCA-like, but were not consistent regarding tumor-infiltrating lymphocytes, CD8 and PD-L1 expression. Conclusions: Although we found that MSI-H was uncommon (0.9%) in TNBCs, potential targets for ICIs exist in TNBCs. Therefore, MSI-H breast cancer patients should be picked up using not only conventional methods but also platforms for comprehensive genomic profiling..
8. Kazuki Takada, Shinkichi Takamori, Yasuto Yoneshima, Kentaro Tanaka, Isamu Okamoto, Mototsugu Shimokawa, Taro Oba, Atsushi Osoegawa, Tetsuzo Tagawa, Mitsuhiro Takenoyama, Yoshinao Oda, Yoichi Nakanishi, Masaki Mori, Serum markers associated with treatment response and survival in non-small cell lung cancer patients treated with anti-PD-1 therapy, Lung Cancer, 10.1016/j.lungcan.2020.04.034, 145, 18-26, 2020.05, Background: Several serum markers have been associated with treatment response and clinical outcome in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. Materials and methods: We performed univariate and multivariate analyses on 226 patients with advanced or recurrent NSCLC treated with anti-programmed cell death-1 (PD-1) therapy. The cut-off values for body mass index (BMI), albumin (Alb), and serum inflammatory markers were determined by receiver operating characteristic curve analyses. Tumor response was assessed by computed tomography according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Results: BMI ≥ 19.1 kg/m2 and derived neutrophil-lymphocyte ratio (dNLR) < 2.79 were independent predictors of overall response, and Alb ≥ 3.5 g/dL and dNLR < 2.79 were independent predictors of disease control. Analyses of survival revealed that Alb < 3.5 g/dL, dNLR ≥ 2.79, lymphocyte-monocyte ratio < 2.12, and red blood cell distribution width ≥ 15.9 % were independent predictors of both progression-free and overall survival. Moreover, these markers tended to have a strong impact on survival, especially among patients with programmed cell death-ligand 1 tumor proportion score ≥ 50 %. Conclusions: dNLR might be the most important factor for predicting the efficacy in NSCLC patients treated with anti-PD-1 therapy..
9. Kenichiro Yahiro, Yoshihiro Matsumoto, Hisakata Yamada, Makoto Endo, Nokitaka Setsu, Toshifumi Fujiwara, Makoto Nakagawa, Atsushi Kimura, Eijiro Shimada, Seiji Okada, Yoshinao Oda, Yasuharu Nakashima, Activation of TLR4 signaling inhibits progression of osteosarcoma by stimulating CD8-positive cytotoxic lymphocytes, Cancer Immunology, Immunotherapy, 10.1007/s00262-020-02508-9, 69, 5, 745-758, 2020.05, Background: Osteosarcoma (OS) is the most common malignant bone tumor and the prognosis of advanced cases is still poor. Recently, there have been several reports suggesting the relationship between innate immunity and OS, but the detailed mechanism is unknown. We demonstrate the relationship between OS and Toll-like receptor 4 (TLR4) which is one of the most important factors in innate immunity. Methods: We established a syngenic mouse tumor model using C3H/HeN, C3H/HeJ mouse and a highly metastatic OS cell line, LM8. TLR4 activation with lipopolysaccharide (LPS) was performed on both mice and its influence on the progression of OS was evaluated. We also performed CD8 + cells depletion to examine the influence on TLR4 activation effects. Results: Tumor volume of C3H/HeN mice was significantly smaller and overall survival of C3H/HeN mice was significantly longer than C3H/HeJ mice. We found more CD8+ cells infiltrating in lung metastases of C3H/HeN mice and depletion of CD8+ cells canceled the antitumor effects of LPS. Conclusion: TLR4 activation by LPS increased CD8+ cells infiltrating into lung metastases and suppressed OS progression in the mouse model. TLR4 activation may suppress the progression of OS via stimulating CD8+ cells and can be expected as a novel treatment for OS..
10. Hirofumi Ohmura, Kyoko Yamaguchi, Fumiyasu Hanamura, Mamoru Ito, Akitaka Makiyama, Keita Uchino, Hozumi Shimokawa, Shingo Tamura, Taito Esaki, Kenji Mitsugi, Yoshihiro Shibata, Hisanobu Oda, Kenji Tsuchihashi, Hiroshi Ariyama, Hitoshi Kusaba, Yoshinao Oda, Koichi Akashi, Eishi Baba, OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody, British journal of cancer, 10.1038/s41416-020-0810-1, 122, 10, 1507-1517, 2020.05, Background: Anti-PD-1 monoclonal antibody, nivolumab, has shown efficacy for advanced gastric cancer (AGC). However, the specific immune cell subsets predominantly activated during the period of anti-PD-1 therapy for AGC have not been clarified. Methods: Peripheral blood of 30 AGC patients treated with nivolumab was prospectively obtained before the initial and second administrations and at the time of progressive disease (PD). The proportions of immune cell subsets and the serum concentrations of cytokines were systematically analysed by flow cytometry. Associations of subsets and serum cytokines with therapeutic effects were evaluated. Results: After the initial administration, significant increases in activated central/effector memory, activated effector T cells, and activated T-helper 1 subsets were observed. At the time of PD, activated regulatory T cells, LAG3-positive CD4+/CD8+ T cells, and TIM3-positive CD4+/CD8+ T cells increased significantly. Significant positive correlations were shown between progression-free survival and proportions of LAG3-positive CD4+/CD8+ T cells and of OX40-positive CD4+/CD8+ T cells (log-rank p = 0.0008, 0.0003, 0.0035 and 0.0040). Conclusions: Nivolumab therapy enhances activation of central/effector memory and effector subsets of CD4+/CD8+ T cells. The expression levels of LAG-3 and OX40 on T cells correlated with the efficacy of nivolumab therapy and could be reasonable biomarkers for anti-PD-1 therapy..
11. Junki Maehara, Yohei Masugi, Tokiya Abe, Hanako Tsujikawa, Yutaka Kurebayashi, Akihisa Ueno, Hidenori Ojima, Shigeo Okuda, Masahiro Jinzaki, Masahiro Shinoda, Yuko Kitagawa, Yoshinao Oda, Hiroshi Honda, Michiie Sakamoto, Quantification of intratumoral collagen and elastin fibers within hepatocellular carcinoma tissues finds correlations with clinico-patho-radiological features, Hepatology Research, 10.1111/hepr.13484, 50, 5, 607-619, 2020.05, Aim: Emerging evidence suggests a promising role for tumor stromal factors in characterizing patients with various types of malignancies, including hepatocellular carcinoma (HCC). We quantified the amount of collagen and elastin fibers in HCC samples with the aim of clarifying the clinico-patho-radiological significance of fiber deposition in HCC. Methods: We computed the amount of collagen and elastin fibers using digital image analysis of whole-slide images of Elastica van Gieson-stained tissues from 156 surgically resected HCCs. Furthermore, we assessed the correlations between the fiber content of HCC samples and clinical, pathological, and radiological features, including immunohistochemistry-based molecular subtypes and immunosubtypes. Results: The intratumoral area ratio of collagen in HCC tissues (median 3.4%, range 0.1–22.2%) was more than threefold that of elastin (median 0.9%, range 0.1–9.0%); there was a strong positive correlation between the amounts of collagen and elastin. Higher levels of combined collagen and elastin were significantly associated with the confluent multinodular macroscopic tumor type, the absence of a fibrous capsule, intratumoral steatosis, scirrhous tumor stroma, dense inflammatory-cell infiltrates, and the biliary/stem cell markers-positive HCC subtype. The associations of higher collagen levels with radiological findings, including heterogeneous enhancement and persistent enhancement on dynamic computed tomography, were significant. In contrast, the associations of radiological findings with elastin fibers were not significant. Intratumoral fibrous stroma in HCC comprised septum-like and perisinusoidal fibrosis; these two forms represented distinct distribution patterns of fibers and fibroblasts. Conclusion: Quantitative analysis suggested that stromal fiber-rich HCCs likely represent a distinct clinico-patho-radiological entity..
12. Kazuki Takada, Gouji Toyokawa, Fumihiko Kinoshita, Tomoko Jogo, Kenichi Kohashi, Sho Wakasu, Yuki Ono, Kensuke Tanaka, Taro Oba, Atsushi Osoegawa, Tetsuzo Tagawa, Koichi Azuma, Isamu Okamoto, Mototsugu Shimokawa, Yoshinao Oda, Masaki Mori, Expression of PD-L1, PD-L2, and IDO1 on tumor cells and density of CD8-positive tumor-infiltrating lymphocytes in early-stage lung adenocarcinoma according to histological subtype, Journal of Cancer Research and Clinical Oncology, 10.1007/s00432-020-03250-6, 2020.05, Purpose: This study examined the expression of programmed cell death-ligand 1 (PD-L1), programmed cell death-ligand 2 (PD-L2), and indoleamine 2,3-dioxygenase-1 (IDO1) in tumor cells and cluster of differentiation 8 (CD8)-positive tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma according to histological subtypes. Methods: We evaluated PD-L1, PD-L2, and IDO1 expression in tumor cells and CD8-positive TILs in surgically resected specimens from 196 stage 0 or I lung adenocarcinoma patients by immunohistochemical staining. We also examined the relationships between the expression of PD-L1, PD-L2, and IDO1 in tumor cells and the density of CD8-positive TILs and clinical factors. Patients were divided into three groups: A, adenocarcinoma in situ and minimally invasive adenocarcinoma (N = 32); B, lepidic predominant invasive adenocarcinoma (IAD; LPA; N = 66); and C, IAD except for LPA (N = 98). Results: PD-L1 was expressed only in Group C, but not in Groups A or B. The positive ratio of PD-L2 was significantly higher in Group C (63.3%), and that of IDO1 was also significantly higher in Group C (65.3%). The density of CD8-positive TILs was significantly higher in Group C (45 ± 2.4). There was no significant difference between the positive ratios of PD-L2 and IDO1 and the density of CD8-positive TILs in Group A (50.0%, 21.9%, and 36 ± 4.1, respectively) or Group B (60.6%, 25.8%, and 44 ± 3.0, respectively). Conclusions: No cases in Groups A and B expressed PD-L1. The expression of immune-related factors, especially PD-L1 and IDO1, was significantly associated with Group C. This is the first report of the detailed examination of PD-L1, PD-L2, IDO1, and CD8 expression in lung adenocarcinoma subtypes with lepidic predominant components. Our results could help identify patients who would benefit from perioperative immunotherapy..
13. Yu Toda, Kenichi Kohashi, Yuichi Yamada, Masato Yoshimoto, Shin Ishihara, Yoshihiro Ito, Takeshi Iwasaki, Hidetaka Yamamoto, Yoshihiro Matsumoto, Yasuharu Nakashima, Masaaki Mawatari, Yoshinao Oda, PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients
comparative study of primary and metastatic lesions, Journal of Cancer Research and Clinical Oncology, 10.1007/s00432-020-03242-6, 2020.05, Purpose: Programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunosuppressive proteins known to be associated with poor prognosis in various cancers. However, their expression and clinical relevance in osteosarcoma remain unknown. In this study, the relationships of PD-L1 and IDO1 expression with clinicopathological features and prognosis were explored. Methods: The expression of PD-L1, IDO1, CD3, CD4, and CD8 in 112 formalin-fixed, paraffin-embedded tumor tissues collected by biopsy or surgical resection from 56 osteosarcoma patients was evaluated immunohistochemically. Moreover, four osteosarcoma cell lines were evaluated for the effects of IFNγ on PD-L1 and IDO1 mRNA expression by real-time reverse-transcription polymerase chain reaction. Results: In pre-neoadjuvant chemotherapy (NAC) primary specimens, 10 cases (17%) showed PD-L1 expression and 12 (21%) showed IDO1 expression. Six of ten cases (60%) with PD-L1 positivity co-expressed IDO1. In post-NAC metastatic lesions, the frequency of immunoexpression of PD-L1 and IDO1 was increased compared with that in pre-NAC specimens. PD-L1 and/or IDO1 expression was not associated with poor prognosis. PD-L1 immunoexpression was significantly associated with the infiltration of CD3+ T cells, CD4+ T cells, and CD8+ T cells; while, IDO1 immunoexpression was significantly associated with the infiltration of CD3+ T cells and CD4+ T cells. In all osteosarcoma cell lines, PD-L1 and IDO1 expression was upregulated by stimulation with IFNγ. Conclusion: Our results suggest that the PD-L1 and IDO1 immune checkpoint inhibitors may provide clinical benefit in osteosarcoma patients with metastatic lesions after conventional chemotherapy..
14. Kyohei Yugawa, Shinji Itoh, Tomoharu Yoshizumi, Shohei Yoshiya, Kazuki Takeishi, Takeo Toshima, Noboru Harada, Toru Ikegami, Kenichi Kohashi, Yoshinao Oda, Masaki Mori, Prognostic impact of 8-hydroxy-deoxyguanosine and its repair enzyme 8-hydroxy-deoxyguanosine DNA glycosylase in hepatocellular carcinoma, Pathology International, 10.1111/pin.12952, 2020.05, Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC..
15. Kodama K, Sonoda K, Kijima M, Yamaguchi S, Yagi H, Yasunaga M, Ohgami T, Onoyama I, Kaneki E, Okugawa K, Yahata H, Ohishi Y, Oda Y, Kato K., Retrospective analysis of treatment and prognosis for uterine leiomyosarcoma: 10-year experience of a single institute., Asia Pac J Clin Oncol., 16 (2):e63-e67, 2020.04.
16. Hidetaka Yamamoto, Yui Nozaki, Kenichi Kohashi, Izumi Kinoshita, Yoshinao Oda, Diagnostic utility of pan-Trk immunohistochemistry for inflammatory myofibroblastic tumours, Histopathology, 10.1111/his.14010, 76, 5, 774-778, 2020.04, Aims: Inflammatory myofibroblastic tumour (IMT) is a spindle cell neoplasm of intermediate malignancy, and the diagnosis is often challenging due to the morphological overlap with other spindle cell neoplasms and reactive lesions. More than half of IMTs have the ALK gene rearrangement, and a minor subset have ROS1, NTRK3 or RET gene rearrangements. We sought to determine the potential diagnostic utility of pan-Trk immunohistochemistry for IMTs. Methods and results: We retrospectively examined 40 cases of IMT using immunohistochemistry with a rabbit monoclonal pan-Trk antibody. Gene rearrangement was confirmed by fluorescence in-situ hybridisation and/or reverse transcription–polymerase chain reaction. The IMTs were classified as the ALK (n = 29), ROS1 (n = 2), NTRK3 (n = 2), RET (n = 0) and ‘quadruple-negative’ (n = 7) genotypes by molecular analyses. Both of the ETV6–NTRK3 fusion-positive cases showed nuclear and cytoplasmic staining for pan-Trk in the majority of tumour cells. None of the ALK, ROS1 or quadruple-negative-type IMTs showed nuclear staining for pan-Trk, but approximately one-third of these IMTs showed focal and weak cytoplasmic staining. One exceptional case of a RANBP2–ALK-positive epithelioid inflammatory myofibroblastic sarcoma (an aggressive variant of IMT) showed moderate cytoplasmic staining for pan-Trk. Conclusions: These results suggest that pan-Trk immunoreactivity with a nuclear and cytoplasmic staining pattern may be useful to identify ETV6–NTRK3-positive IMTs and may be helpful in selecting patients for Trk-targeted therapy..
17. Youran Zou, Gulisa Turashvili, Robert A. Soslow, Kay J. Park, Sabrina Croce, W. Glenn McCluggage, Colin J.R. Stewart, Yoshinao Oda, Esther Oliva, Robert H. Young, Arnaud Da Cruz Paula, Kimberly Dessources, Charles W. Ashley, Martee L. Hensley, Stephen Yip, Britta Weigelt, Ryma Benayed, Cristina R. Antonescu, Cheng Han Lee, Sarah Chiang, High-grade transformation of low-grade endometrial stromal sarcomas lacking YWHAE and BCOR genetic abnormalities, Modern Pathology, 10.1038/s41379-020-0535-y, 2020.04, High-grade histologic transformation of low-grade endometrial stromal sarcoma (LGESS) is rare. Here, we describe the clinicopathologic features and gene fusion status of 12 cases (11 primary uterine corpus and 1 primary vaginal), 11 diagnosed prospectively from 2016, and 1 retrospectively collected. Targeted RNA sequencing and/or fluorescence in situ hybridization was employed in all cases. High-grade transformation was seen at the time of initial diagnosis in eight patients and at the time of recurrence in four patients, 4–11 years after initial diagnosis of LGESS. High-grade morphology consisted of generally uniform population of round to epithelioid cells with enlarged nuclei one to two times larger than a lymphocyte, visible nucleoli, and increased mitotic index (range, 6–30; median, 16 per 10 high-power fields); there was often an associated sclerotic and/or myxoid stroma. Estrogen receptor, progesterone receptor, and CD10 expression was absent or significantly decreased (compared with the low-grade component) in the high-grade foci of five tumors. One tumor demonstrated positive (diffuse and strong) cyclin D1 and BCOR staining. p53 staining was wild type in both components of all eight tumors tested. JAZF1-SUZ12 (n = 6), JAZF1-PHF1 (n = 3), EPC1-PHF1, (n = 1), or BRD8-PHF1 (n = 1) fusions were detected in 11 tumors; no fusions were found in one by targeted RNA sequencing. Patients presented with FIGO stages I (n = 4), II (n = 4), III (n = 1), and IV disease (n = 2). Median overall survival calculated from the time of histologic transformation was 22 months (range, 8 months to 8 years) with five patients who died of disease 8–18 months after transformation. High-grade transformation may occur in LGESS with JAZF1 and PHF1 rearrangements at the time of or years after initial diagnosis. Such high-grade transformation is characterized by nuclear enlargement, prominent nucleoli, and increased mitotic index compared with typical LGESS. Histologic high-grade transformation may herald aggressive behavior..
18. Nao Fujimori, Masami Miki, Lingaku Lee, Kazuhide Matsumoto, Yu Takamatsu, Takehiro Takaoka, Katsuhito Teramatsu, Yuta Suehiro, Masatoshi Murakami, Hisato Igarashi, Takamasa Oono, Takao Ohtsuka, Masafumi Nakamura, Yutaka Koga, Yoshinao Oda, Tetsuhide Ito, Yoshihiro Ogawa, Natural history and clinical outcomes of pancreatic neuroendocrine neoplasms based on the WHO 2017 classification; a single-center experience of 30 years, Pancreatology, 10.1016/j.pan.2020.04.003, 2020.04, Background/Objectives: This single-center study aimed to evaluate treatment outcomes and long-term prognosis of patients with pancreatic neuroendocrine neoplasms (PanNENs) based on the World Health Organization (WHO) 2017 classification. Methods: We enrolled 245 patients with PanNENs treated at Kyushu University Hospital between January 1987 and March 2018. PanNENs were categorized according to the WHO 2017 classification or further subdivisions of Ki-67 index. Clinicopathological features, median survival time (MST), and prognostic factors were retrospectively analyzed. Results: The number of PanNENs, especially non-functioning PanNENs, has increased over the last decade. The mean MST of all patients was 202 months; which was longest in patients with NET G1 (n = 145, MST = 261 months) relative to NET G2 (n = 72, 132 months), NET G3 (n = 3, 34 months) and NEC G3 (n = 17, 9 months). Prognosis in patients with surgery as the first-line treatment was significantly better than in those with drug therapy. However, 26% of patients who underwent curative resection developed recurrence after a median time of 28.7 months. In unresectable PanNENs (n = 97), the MST and 5-year survival rate were 78 months and 55.8%, respectively. Poor differentiation, Ki-67 index of >10% and presence of liver metastasis were significant unfavorable predictors. Response to first-line therapy (stable disease/partial response) and three or more treatment regimens were significant favorable predictors for unresectable PanNENs according to multivariate analyses (p < 0.01). Conclusions: We demonstrated the utility of the WHO 2017 classification for PanNENs in the real clinical setting. For better prognosis in PanNENs, the use of three or more regimens should be considered..
19. Masato Yoshimoto, Yuichi Yamada, Shin Ishihara, Kenichi Kohashi, Yu Toda, Yoshihiro Ito, Yosuke Susuki, Izumi Kinoshita, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda, Retroperitoneal Myxofibrosarcoma
A Controversial Entity, Pathology Research and Practice, 10.1016/j.prp.2020.152969, 2020.04.
20. Jiromaru R, Yamamoto H, Yasumatsu R, Hongo T, Nozaki Y, Hashimoto K, Taguchi K, Masuda M, Nakagawa T, Oda Y., HPV-related Sinonasal Carcinoma: Clinicopathologic Features, Diagnostic Utility of p16 and Rb Immunohistochemistry, and EGFR Copy Number Alteration., Am J Surg Pathol., 44(3):305-315, 2020.03.
21. Basturk O, Weigelt B, Adsay V, Benhamida JK, Askan G, Wang L, Arcila ME, Zamboni G, Fukushima N, Gularte-Mérida R, Da Cruz Paula A, Selenica P, Kumar R, Pareja F, Maher CA, Scholes J, Oda Y, Santini D, Doyle LA, Petersen I, Flucke U, Koelsche C, Reynolds SJ, Yavas A, Deimling AV, Reis-Filho JS, Klimstra DS., Sclerosing epithelioid mesenchymal neoplasm of the pancreas - a proposed new entity., Mod Pathol., 33 (3):456-467, 2020.03.
22. Shinichi Tsuruta, Kenichi Kohashi, Yuichi Yamada, Minako Fujiwara, Yutaka Koga, Eikichi Ihara, Yoshihiro Ogawa, Eiji Oki, Masafumi Nakamura, Yoshinao Oda, Solid-type poorly differentiated adenocarcinoma of the stomach
Deficiency of mismatch repair and SWI/SNF complex, Cancer Science, 10.1111/cas.14301, 111, 3, 1008-1019, 2020.03, ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid-type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid-type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid-type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid-type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid-type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid-type PDAs. In the MMR-deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P =.0268, P =.0181, P =.0224, and P =.0071, respectively). In the MMR-proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P =.012). In conclusion, solid-type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated-type adenocarcinoma to solid-type PDA..
23. Tsuyoshi Iwanaka, Takayoshi Yamaza, Soichiro Sonoda, Koichiro Yoshimaru, Toshiharu Matsuura, Haruyoshi Yamaza, Shouichi Ohga, Yoshinao Oda, Tomoaki Taguchi, A model study for the manufacture and validation of clinical-grade deciduous dental pulp stem cells for chronic liver fibrosis treatment, Stem Cell Research and Therapy, 10.1186/s13287-020-01630-w, 11, 1, 2020.03, Background: Human deciduous pulp stem cells (hDPSCs) have remarkable stem cell potency associated with cell proliferation, mesenchymal multipotency, and immunosuppressive function and have shown beneficial effects in a variety of animal disease models. Recent studies demonstrated that hDPSCs exhibited in vivo anti-fibrotic and anti-inflammatory action and in vivo hepatogenic-associated liver regeneration, suggesting that hDPSCs may offer a promising source with great clinical demand for treating liver diseases. However, how to manufacture ex vivo large-scale clinical-grade hDPSCs with the appropriate quality, safety, and preclinical efficacy assurances remains unclear. Methods: We isolated hDPSCs from human deciduous dental pulp tissues formed by the colony-forming unit-fibroblast (CFU-F) method and expanded them under a xenogeneic-free and serum-free (XF/SF) condition; hDPSC products were subsequently stored by two-step banking including a master cell bank (MCB) and a working cell bank (WCB). The final products were directly thawed hDPSCs from the WCB. We tested the safety and quality check, stem cell properties, and preclinical potentials of final hDPSC products and hDPSC products in the MCB and WCB. Results: We optimized manufacturing procedures to isolate and expand hDPSC products under a XF/SF culture condition and established the MCB and the WCB. The final hDPSC products and hDPSC products in the MCB and WCB were validated the safety and quality including population doubling ability, chromosome stability, microorganism safety, and stem cell properties including morphology, cell surface marker expression, and multipotency. We also evaluated the in vivo immunogenicity and tumorigenicity and validated in vivo therapeutic efficacy for liver regeneration in a CCl4-induced chronic liver fibrosis mouse model in the final hDPSC products and hDPSC products in the WCB. Conclusion: The manufacture and quality control results indicated that the present procedure could produce sufficient numbers of clinical-grade hDPSC products from a tiny deciduous dental pulp tissue to enhance clinical application of hDPSC products in chronic liver fibrosis..
24. Ito T, Kaku-Ito Y, Murata M, Furue K, Shen C, Oda Y, Furue M. , Immunohistochemical BRAF V600E Expression and Intratumor BRAF V600E Heterogeneity in Acral Melanoma: Implication in Melanoma-Specific Survival. , J Clin Med. , 9(3), 2020.03.
25. Hori Y, Yamamoto H, Nozaki Y, Torisu T, Fujiwara M, Taguchi K, Nishiyama K, Nakamura S, Kitazono T, Oda Y., Colorectal diffuse large B-cell lymphoma: molecular subclassification and prognostic significance of immunoglobulin gene translocation., Hum Pathol., 96:67-78, 2020.02.
26. Hossain A, Arimura H, Kinoshita F, Ninomiya K, Watanabe S, Imada K, Koyanagi R, Oda Y., Automated approach for estimation of grade groups for prostate cancer based on histological image feature analysis., Prostate., 2020.02.
27. Alamgir Hossain, Hidetaka Arimura, Fumio Kinoshita, Kenta Ninomiya, Sumiko Watanabe, Kenjiro Imada, Ryoma Koyanagi, Yoshinao Oda, Automated approach for estimation of grade groups for prostate cancer based on histological image feature analysis, Prostate, 10.1002/pros.23943, 80, 3, 291-302, 2020.02, Background: There is a low reproducibility of the Gleason scores that determine the grade group of prostate cancer given the intra- and interobserver variability among pathologists. This study aimed to develop an automated approach for estimating prostate cancer grade groups based on features obtained from histological image analysis. Methods: Fifty-nine patients who underwent radical prostatectomy were selected under the approval of the institutional review board of our university hospital. For estimation, we followed the grade group criteria provided by the International Society of Urological Pathology in 2014. One hundred eight specimen slides obtained from the patients were digitized to extract 110 regions of interest (ROI) from hematoxylin and eosin-stained histological images using a digital whole slide scanner at ×20 magnification with a pixel size of 0.4 μm. Each color pixel value in the ROI was decomposed into six intensities corresponding to the RGB (red, green, and blue) and HSV (hue, saturation, and value) color models. Image features were extracted by histological image analysis, obtaining 54 features from the ROI based on histogram and texture analyses in the six types of decomposed histological images. Then, 40 representative features were selected from the 324 histological image features based on statistically significant differences (P <.05) between the mean image feature values for high (≥3, Gleason score ≥4 + 3) and low (≤2, Gleason score ≤3 + 4) grade groups. The relationship between grade groups and the most representative image feature (ie, complexity) was approximated using regression to estimate real-number grade groups defined by continuous numerical grading. Finally, the grade groups were expressed as the conventional grade groups (ie, integers from 1 to 5) using a piecewise step function. Results: The grade groups were correctly estimated by the proposed approach without errors on training (70 ROIs) and validation (40 ROIs) data. Conclusions: Our results suggest that the proposed approach may support pathologists during the evaluation of grade groups for prostate cancer, thus mitigating intra- and interobserver variability..
28. Kiyoshi Saeki, Hideya Onishi, Satoko Koga, Shu Ichimiya, Kazunori Nakayama, Yasuhiro Oyama, Makoto Kawamoto, Kukiko Sakihama, Takeo Yamamoto, Ryota Matsuda, Yoshihiro Miyasaka, Masafumi Nakamura, Yoshinao Oda, FAM115C could be a novel tumor suppressor associated with prolonged survival in pancreatic cancer patients, Journal of Cancer, 10.7150/jca.38399, 11, 8, 2289-2302, 2020.02, Hypoxia is a characteristic feature of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). We have recently explored new targeting molecules and pathways in PDAC cells under hypoxic conditions. In this study, we performed a microarray experiment to analyze the genes up-regulated in PDAC cell lines under hypoxia compared to normoxia, and identified human family with sequence similarity 115, member C (FAM115C) as a candidate gene for further study. Our data showed that FAM115C was overexpressed in PDAC cell lines under hypoxia, and FAM115C inhibition promoted PDAC cell migration and invasion in vitro. FAM115C inhibition did not affect tumor cell proliferation in PDAC. Immunohistochemically, FAM115C expression was observed ubiquitously in normal pancreas, pancreatic intraepithelial neoplasia (PanIN) and PDAC tissue, and it was located mainly in the nucleus but also in the cytoplasm of cells. In qPCR analysis, high expression of FAM115C was correlated with better prognosis in patients with PDAC. Our findings suggest that FAM115C could be a novel tumor suppressor associated with prolonged survival in patients with PDAC..
29. Jun Inaishi, Yoshifumi Saisho, Yoichiro Hirakawa, Daigo Yoshida, Jun Hata, Naoko Mukai, Yuusuke Watanabe, Yoshinao Oda, Hiroshi Itoh, Toshiharu Ninomiya, Association of glucose tolerance status with pancreatic β- and α-cell mass in community-based autopsy samples of Japanese individuals
The Hisayama Study, Journal of Diabetes Investigation, 10.1111/jdi.13232, 2020.02, Aims/Introduction: Changes in histologically quantified β- and α-cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in β- and α-cell mass according to the glucose tolerance status. Materials and Methods: Autopsy samples from a total of 103 individuals (40 with normal glucose tolerance, 31 with prediabetes and 32 with type 2 diabetes mellitus) who underwent a 75-g oral glucose tolerance test within 5 years before death were selected from 643 community-based autopsy samples collected from 2002 to 2016. Fractional β-cell area (BCA) and α-cell area were quantified with Image Pro Plus software. Associations of BCA and α-cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman’s correlation coefficients between glycemic markers and β-cell function were estimated. Results: The mean values of BCA decreased significantly with worsening glucose tolerance status (mean ± standard error 1.85 ± 0.10% in normal glucose tolerance, 1.59 ± 0.11% in prediabetes and 1.17 ± 0.11% in type 2 diabetes mellitus, P for trend < 0.001), whereas there was no significant association between α-cell area and glucose tolerance status. BCA was inversely correlated with fasting and 2-h plasma glucose levels during oral glucose tolerance test and glycated hemoglobin measurement, and positively correlated with disposition index (all P < 0.01). Conclusions: β-Cell mass decreased significantly with worsening glucose tolerance, from the stage of prediabetes, in the Japanese population. Prevention of declining β-cell mass before the onset of glucose intolerance is important to reduce the burden of type 2 diabetes mellitus..
30. Kyoko Yamaguchi, Mamoru Ito, Hirofumi Ohmura, Fumiyasu Hanamura, Michitaka Nakano, Kenji Tsuchihashi, Shuntaro Nagai, Hiroshi Ariyama, Hitoshi Kusaba, Hidetaka Yamamoto, Yoshinao Oda, Masafumi Nakamura, Koichi Akashi, Eishi Baba, Helper T cell-dominant tertiary lymphoid structures are associated with disease relapse of advanced colorectal cancer, OncoImmunology, 10.1080/2162402X.2020.1724763, 9, 1, 2020.02, Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient’s prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3+ Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition..
31. Itoh S, Yoshizumi T, Yugawa K, Imai D, Yoshiya S, Takeishi K, Toshima T, Harada N, Ikegami T, Soejima Y, Kohashi K, Oda Y, Mori M. , Impact of Immune Response on Outcomes in Hepatocellular Carcinoma: Association With Vascular Formation. , Hepatology. , 2020.02.
32. Yoshimoto M, Yamada Y, Ishihara S, Kohashi K, Toda Y, Ito Y, Yamamoto H, Furue M, Nakashima Y, Oda Y., Comparative Study of Myxofibrosarcoma With Undifferentiated Pleomorphic Sarcoma: Histopathologic and Clinicopathologic Review., Am J Surg Pathol., 44(1):87-97, 2020.01.
33. Hiramoto T, Tahara M, Liao J, Soda Y, Miura Y, Kurita R, Hamana H, Inoue K, Kohara H, Miyamoto S, Hijikata Y, Okano S, Yamaguchi Y, Oda Y, Ichiyanagi K, Toh H, Sasaki H, Kishi H, Ryo A, Muraguchi A, Takeda M, Tani K., Non-transmissible MV Vector with Segmented RNA Genome Establishes Different Types of iPSCs from Hematopoietic Cells., Mol Ther., 28(1):129-141, 2020.01.
34. Ohmura H, Ito M, Uchino K, Okada C, Tanishima S, Yamada Y, Momosaki S, Komoda M, Kuwayama M, Yamaguchi K, Okumura Y, Nakano M, Tsuchihashi K, Isobe T, Ariyama H, Kusaba H, Oda Y, Akashi K, Baba E., Methylation of drug resistance-related genes in chemotherapy-sensitive Epstein-Barr virus-associated gastric cancer., FEBS Open Bio., 10(1):147-157, 2020.01.
35. Tamaki Ueda, Yuhki Koga, Hiroshi Yoshikawa, Mika Tanabe, Kanako Yamana, Utako Oba, Kentaro Nakashima, Hiroaki Ono, Takuya Ichimura, Shunji Hasegawa, Wakako Kato, Tetsuko Kobayashi, Hideki Nakayama, Yasunari Sakai, Tadamasa Yoshitake, Saiji Ohga, Yoshinao Oda, Shigenobu Suzuki, Koh Hei Sonoda, Shouichi Ohga, Survival and ocular preservation in a long-term cohort of Japanese patients with retinoblastoma, BMC Pediatrics, 10.1186/s12887-020-1923-7, 20, 1, 2020.01, Background: Retinoblastoma is an ocular tumor in infants with cancer predisposition. Treatment of the rare tumor needs to be optimized for ocular preserved survival without second primary malignancy (SPM). Methods: We studied the outcomes of all patients with retinoblastoma at a tertiary center in 1984-2016, when preservation method changed from radiotherapy (1984-2001) to systemic chemotherapy (2002-2016). Results: One-hundred sixteen infants developed unilateral- (n = 77), bilateral- (n = 38), or trilateral-onset (n = 1) tumor. Ten (8.6%) had a positive family history, despite a few studies on RB1 gene. Contralateral disease occurred in one unilateral-onset case. One-hundred eight of 155 eyes (70%) were enucleated. Nine binocular survivors were from 5 bilateral- and 4 unilateral-onset cases. Two survivors received bilateral enucleation. Six deaths occurred; brain involvement (including 3 trilateral diseases) in 4 bilateral-onset, systemic invasion in a unilateral-onset, and SPM (osteosarcoma) in a bilateral-onset case(s). Two others survived SPM of osteosarcoma or lymphoma. The 10-year overall survival (OS: 98.5% vs. 91.3%, p = 0.068) and binocular survivors (13.2% vs. 5.2%, p = 0.154) between bilateral- and unilateral-onsets did not differ statistically. The 10-year OS and cancer (retinoblastoma/SPM)-free survival (CFS) rates of all patients were 94.9 and 88.5%, respectively. The proportion of preserved eyes did not differ between radiotherapy and chemotherapy eras. The CFS rate of bilateral-onset cases in systemic chemotherapy era was higher than that in radiotherapy era (p = 0.042). The CFS rates of bilateral-onset patients with neoadjuvant chemotherapy (upfront systemic therapy for preservation) was higher than those without it (p = 0.030). Conclusions: Systemic chemotherapy and local therapy raised OS and binocular survival rates of bilateral-onset patients similarly to those of unilateral-onset patients. All but one death was associated with a probable germline defect of the RB1 gene. Neoadjuvant stratified chemotherapy may support the long-term binocular life with minimized risk of SPM..
36. Yohei Ando, Kenoki Ohuchida, Yoshiki Otsubo, Shin Kibe, Shin Takesue, Toshiya Abe, Chika Iwamoto, Koji Shindo, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Takao Ohtsuka, Yoshinao Oda, Masafumi Nakamura, Necroptosis in pancreatic cancer promotes cancer cell migration and invasion by release of CXCL5, PloS one, 10.1371/journal.pone.0228015, 15, 1, 2020.01, Background Necroptosis is a form of programmed cell death that is accompanied by release of intracellular contents, and reportedly contributes to various diseases. Here, we investigate the significance of necroptosis in pancreatic cancer. Methods We used immunohistochemistry and western blot analysis to evaluate expression of the key mediators of necroptosis—receptor-interacting serine/threonine protein kinase 3 (RIP3) and mixed lineage kinase domain-like (MLKL)—in human pancreatic cancer. We also tested the effects of conditioned media (CM) from necroptotic cells on pancreatic cancer cells in Transwell migration and Matrigel invasion assays. Protein array analysis was used to investigate possible mediators derived from necroptotic cells. Results RIP3 and MLKL are highly expressed in human pancreatic cancer tissues compared with normal pancreas. MLKL expression was particularly intense at the tumor invasion front. CM derived from necroptotic cells promoted cancer cell migration and invasion, but not CM derived from apoptotic cells. C-X-C motif chemokine 5 (CXCL5) was upregulated in CM derived from necroptotic cells compared with CM derived from control or apoptotic cells. Moreover, expression of the receptor for CXCL5, C-X-C-motif chemokine receptor-2 (CXCR2), was upregulated in pancreatic cancer cells. Inhibition of CXCR2 suppressed cancer cell migratory and invasive behavior enhanced by necroptosis. Conclusion These findings indicate that necroptosis at the pancreatic cancer invasion front can promote cancer cell migration and invasion via the CXCL5–CXCR2 axis..
37. Yusuke Tsuda, Makoto Hirata, Kotoe Katayama, Toru Motoi, Daisuke Matsubara, Yoshinao Oda, Masashi Fujita, Hiroshi Kobayashi, Hirotaka Kawano, Yoshihiro Nishida, Tomohisa Sakai, Tomotake Okuma, Takahiro Goto, Koichi Ogura, Akira Kawai, Keisuke Ae, Ukei Anazawa, Yoshiyuki Suehara, Shintaro Iwata, Satoru Miyano, Seiya Imoto, Tatsuhiro Shibata, Hidewaki Nakagawa, Rui Yamaguchi, Sakae Tanaka, Koichi Matsuda, Massively parallel sequencing of tenosynovial giant cell tumors reveals novel CSF1 fusion transcripts and novel somatic CBL mutations, International Journal of Cancer, 10.1002/ijc.32421, 145, 12, 3276-3284, 2019.12, Tenosynovial giant cell tumor (TSGCT) is a rare neoplasm. Although surgical resection is the widely accepted primary treatment for TSGCT, recurrences are frequent, and patients’ joint function may be severely compromised. Previous studies reported that CSF1-COL6A3 fusion genes were identified in approximately 30% of TSGCTs. The aim of our study was to comprehensively clarify the genomic abnormalities in TSGCTs. We performed whole exome sequencing in combination with target sequence validation on 34 TSGCT samples. RNA sequencing was also performed on 18 samples. RNA sequencing revealed fusion transcripts involving CSF1, including novel CSF1-VCAM1, CSF1-FN1 and CSF1-CDH1 fusions, in 13/18 (72%) cases. These fusion genes were validated by chromogenic in situ hybridization. All CSF1 fusions resulted in the deletion of CSF1 exon 9, which was previously shown to be an important negative regulator of CSF1 expression. We also found that 12 (35%) of the 34 TSGCT samples harbored CBL missense mutations. All mutations were detected in exons 8 or 9, which encode the linker and RING finger domain. Among these mutations, C404Y, L380P and R420Q were recurrent. CBL-mutated cases showed higher JAK2 expression than wild-type CBL cases (p = 0.013). CSF1 fusion genes and CBL mutations were not mutually exclusive, and both alterations were detected in six of the 18 (33%) tumors. The frequent deletion of CSF1 exon 9 in the fusion transcripts suggested the importance of this event in the etiology of TSGCT. Our results may contribute to the development of new targeted therapies using JAK2 inhibitors for CBL-mutated TSGCT..
38. Takamichi Ito, Yumiko Kaku-Ito, Maho Murata, Toshio Ichiki, Yuki Kuma, Yuka Tanaka, Taketoshi Ide, Fumitaka Ohno, Maiko Wada-Ohno, Yuichi Yamada, Yoshinao Oda, Masutaka Furue, Intra-and inter-tumor braf heterogeneity in acral melanoma
An immunohistochemical analysis, International journal of molecular sciences, 10.3390/ijms20246191, 20, 24, 2019.12, The current development of BRAF inhibitors has revolutionized the treatment of unresectable melanoma. As the potential heterogeneity of BRAF mutations in melanoma has been reported, accurate detection of BRAF mutations are important. However, the genetic heterogeneity of acral melanoma—a distinct type of melanoma with a unique genetic background—has not fully been investigated. We conducted a retrospective review of our acral melanoma patients. Of the 196 patients with acral melanoma, we retrieved 31 pairs of primary and matched metastatic melanomas. We immunostained the 31 pairs with VE1, a BRAFV600E-mutation-specific monoclonal antibody. Immunohistochemistry with VE1 showed a high degree of sensitivity and specificity for detecting BRAFV600E mutations compared with the real-time polymerase chain reaction method. A total of nine primary (29.0%) and eight metastatic (25.8%) acral melanomas were positive for VE1. In three patients (9.7%), we observed a discordance of VE1 staining between the primary and metastatic lesions. Of note, VE1 immunohistochemical staining revealed a remarkable degree of intra-tumor genetic heterogeneity in acral melanoma. Our study reveals that VE1 immunostaining is a useful ancillary method for detecting BRAFV600E mutations in acral melanoma and allows for a clear visualization of intra-and inter-tumor BRAF heterogeneity..
39. Ryo Murayama, Akihiro Nishie, Tomoyuki Hida, Shingo Baba, Junichi Inokuchi, Yoshinao Oda, Hiroshi Honda, Uptake of 18F-FDG in Adrenal Adenomas Is Associated With Unenhanced CT Value and Constituent Cells, Clinical nuclear medicine, 10.1097/RLU.0000000000002759, 44, 12, 943-948, 2019.12, PURPOSE: The purposes of this study were to investigate the correlation between unenhanced CT attenuation values and F-FDG uptake in adrenal adenomas, and to clarify the mechanism of FDG uptake in adrenal adenomas based on immunohistochemical findings. MATERIALS AND METHODS: In 57 adrenal adenomas, the correlation between SUVmax on F-FDG PET and unenhanced CT attenuation was retrospectively investigated. In the 11 surgically resected nodules, the clear cell ratio (CCR) and expression levels of glucose transporters (GLUTs) 1 to 4 were pathologically evaluated. The GLUT expression levels were scored at 0 to 3 points for each transporter, and the sum of these expression levels was defined as the GLUT score. The relationships between CCR and either the CT attenuation number or SUVmax, and between the GLUT score and each of the CT attenutation value, SUVmax, or CCR were evaluated. RESULTS: There was a significant positive correlation between SUVmax and the CT attenuation value for the group of 57 adenomas (R = 0.44, P = 0.0007). For the 11 surgically resected cases, there was a nonsignificant trend of negative correlation between SUVmax and CCR (R = 0.57, P = 0.06). There was a significant positive correlation between GLUT score and CT attenuation value (R = 0.68, P = 0.02), and a significant negative correlation between GLUT score and CCR (R = 0.60, P = 0.003). CONCLUSIONS: Adrenal adenomas composed of many compact cells or having high attenuation on unenhanced CT showed high FDG uptake. FDG uptake of adrenal adenomas may depend on the constituent cells..
40. Makoto Hirata, Naofumi Asano, Kotoe Katayama, Akihiko Yoshida, Yusuke Tsuda, Masaya Sekimizu, Sachiyo Mitani, Eisuke Kobayashi, Motokiyo Komiyama, Hiroyuki Fujimoto, Takahiro Goto, Yukihide Iwamoto, Norifumi Naka, Shintaro Iwata, Yoshihiro Nishida, Toru Hiruma, Hiroaki Hiraga, Hirotaka Kawano, Toru Motoi, Yoshinao Oda, Daisuke Matsubara, Masashi Fujita, Tatsuhiro Shibata, Hidewaki Nakagawa, Robert Nakayama, Tadashi Kondo, Seiya Imoto, Satoru Miyano, Akira Kawai, Rui Yamaguchi, Hitoshi Ichikawa, Koichi Matsuda, Integrated exome and RNA sequencing of dedifferentiated liposarcoma, Nature communications, 10.1038/s41467-019-13286-z, 10, 1, 2019.12, The genomic characteristics of dedifferentiated liposarcoma (DDLPS) that are associated with clinical features remain to be identified. Here, we conduct integrated whole exome and RNA sequencing analysis in 115 DDLPS tumors and perform comparative genomic analysis of well-differentiated and dedifferentiated components from eight DDLPS samples. Several somatic copy-number alterations (SCNAs), including the gain of 12q15, are identified as frequent genomic alterations. CTDSP1/2-DNM3OS fusion genes are identified in a subset of DDLPS tumors. Based on the association of SCNAs with clinical features, the DDLPS tumors are clustered into three groups. This clustering can predict the clinical outcome independently. The comparative analysis between well-differentiated and dedifferentiated components identify two categories of genomic alterations: shared alterations, associated with tumorigenesis, and dedifferentiated-specific alterations, associated with malignant transformation. This large-scale genomic analysis reveals the mechanisms underlying the development and progression of DDLPS and provides insights that could contribute to the refinement of DDLPS management..
41. Yuka Kozuma, Gouji Toyokawa, Yuichi Yamada, Fumihiro Shoji, Koji Yamazaki, Yoshinao Oda, Sadanori Takeo, Spread through air spaces in lung neuroendocrine tumor, Translational Lung Cancer Research, 10.21037/tlcr.2019.10.20, 8, S439-S442, 2019.12.
42. Komori K, Ihara E, Minoda Y, Ogino H, Sasaki T, Fujiwara M, Oda Y, Ogawa Y. , The Altered Mucosal Barrier Function in the Duodenum Plays a Role in the Pathogenesis of Functional Dyspepsia., Dig Dis Sci. , (64)11:3228-3239, 2019.11.
43. Mano Y, Yoshio S, Shoji H, Tomonari S, Aoki Y, Aoyanagi N, Okamoto T, Matsuura Y, Osawa Y, Kimura K, Yugawa K, Wang H, Oda Y, Yoshizumi T, Maehara Y, Kanto T. , Bone morphogenetic protein 4 provides cancer-supportive phenotypes to liver fibroblasts in patients with hepatocellular carcinoma. , J Gastroenterol. , 54(11):1007-1018
, 2019.11.
44. Tsutsumi Y, Shiogama K, Teramoto H, Aishima S, Oda Y, Ohashi R, Ajioka Y, Naito M. , Detection of Hepatitis Virus B And C in Archival Autopsy Specimens of Liver Cirrhosis., Biomed J Sci &Tech Res., 22(3):16699-16704
, 2019.11.
45. Yuichi Yamada, Kenichi Kohashi, Izumi Kinoshita, Hidetaka Yamamoto, Takeshi Iwasaki, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yoshihiro Itou, Yutaka Koga, Mikiko Hashisako, Yui Nozaki, Daisuke Kiyozawa, Daichi Kitahara, Takeshi Inoue, Munenori Mukai, Yumi Honda, Gouji Toyokawa, Kenji Tsuchihashi, Yoshifumi Matsushita, Fumiyoshi Fushimi, Kenichi Taguchi, Sadafumi Tamiya, Yumi Oshiro, Masutaka Furue, Yasuharu Nakashima, Satoshi Suzuki, Toru Iwaki, Yoshinao Oda, Clinicopathological review of solitary fibrous tumors
dedifferentiation is a major cause of patient death, Virchows Archiv, 10.1007/s00428-019-02622-9, 475, 4, 467-477, 2019.10, Solitary fibrous tumor (SFT) is a soft-tissue neoplasm of intermediate malignant potential, presenting a wide histopathological spectrum. Poorer prognosis of hemangiopericytoma of the central nervous system (CNS), hypoglycemic SFT, and dedifferentiation are well-known characters of SFT, but their clinical significance were not demonstrated enough by large-sized study. Here, the clinicopathological features of SFTs are reviewed and the relationship between genetics and clinicopathological features is examined using 145 SFT cases. All cases were STAT6 IHC-positive and/or NAB2-STAT6 fusion gene-positive. Tumor location was classified into three categories: 30 pleuropulmonary, 96 non-pleuropulmonary/non-central nervous system (CNS), and 18 CNS tumors. The tumor developed recurrence in 21 of 93 available cases (22.5%), metastasis in 11 of 93 (11.8%), and tumor death in 9 of 93 (9.6%). Hypoglycemia occurred in 2 primary tumors and 1 metastatic tumor among 63 reviewable cases, and dedifferentiation occurred in 10 cases (6.8%) including 6 primary tumors, 2 recurrent tumors, and 2 metastatic tumors. Recurrence was positively associated with CNS location (p = 0.0109) and hypoglycemia (p = 0.001); metastasis was positively associated with CNS location (p = 0.0231), hypoglycemia (p < 0.0001), and dedifferentiation (p < 0.0001), while metastasis was negatively correlated with pleural location (p = 0.0471). Tumor death was positively associated with male sex (p = 0.0154), larger size (p = 0.0455), hypoglycemia (p < 0.0001), and dedifferentiation (p < 0.0001). Multivariate analysis revealed independent statistical significance of dedifferentiation for overall survival (p = 0.0467). Exon variant of the fusion gene had no statistical correlation with clinical outcome. In conclusion, dedifferentiation is a major prognostic factor of SFT, and specific location such as cerebromeningeal and intra-abdominal site and hypoglycemia also had a high risk for unfavorable prognosis..
46. Kensuke Izumaru, Jun Hata, Toshiaki Nakano, Yutaka Nakashima, Masaharu Nagata, Masayo Fukuhara, Yoshinao Oda, Takanari Kitazono, Toshiharu Ninomiya, Reduced Estimated GFR and Cardiac Remodeling
A Population-Based Autopsy Study, American Journal of Kidney Diseases, 10.1053/j.ajkd.2019.02.013, 74, 3, 373-381, 2019.09, Rationale & Objective: Evidence suggests that cardiac remodeling, including left ventricular hypertrophy and myocardial fibrosis, develops with progression of kidney disease. Few studies have examined cardiac pathology across a range of estimated glomerular filtration rates (eGFRs), which was the objective of this investigation. Study Design: Population-based cross-sectional study of deceased patients undergoing autopsy. Setting & Participants: 334 of 694 consecutive deceased patients undergoing autopsy with available cardiac tissue, with a prior health examination within 6 years and without a prior diagnosis of heart disease. Exposure: eGFR. Outcomes: The thickness of the left ventricular wall, sizes of cardiac cells, and percentages of fibrosis, estimated from pathology examination of autopsy samples. Analytical Approach: Generalized estimating equations. Results: Lower eGFRs were associated with greater left ventricular wall thickness. Deceased patients with eGFRs ≥ 60, 45 to 59, 30 to 44, and <30 mL/min/1.73 m2 had left ventricular wall thicknesses of 9.1, 9.5, 9.8, and 10.3 mm, respectively (P for trend < 0.05). Lower eGFRs were also significantly associated with greater mean values of cardiac cell size in the left ventricular wall after adjusting for confounders: 15.3, 16.1, 16.4, and 17.4 μm for eGFRs ≥ 60, 45 to 59, 30 to 44, and <30 mL/min/1.73 m2 (P for trend < 0.01). Patients with lower eGFRs had significantly higher multivariable-adjusted geometric mean values for fibrosis percentage in the left ventricular wall: 3.22%, 4.33%, 3.83%, and 6.14% for eGFRs ≥ 60, 45 to 59, 30 to 44, and <30 mL/min/1.73 m2 (P for trend < 0.001). The negative association of eGFR with multivariable-adjusted mean values of cardiac cell width was stronger among patients with than those without anemia. Limitations: Cross-sectional study with a high proportion of elderly patients, no available information for severity or duration of hypertension and other cardiovascular risk factors, no information for medication use. Conclusions: These findings suggest that reduced eGFR is associated with cardiac hypertrophy and fibrosis of the left ventricle, cardiac cell enlargement, and cardiac fibrosis..
47. Daisuke Imai, Tomoharu Yoshizumi, Shinji Okano, Shinji Itoh, Toru Ikegami, Noboru Harada, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara, IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer, Journal of Surgical Research, 10.1016/j.jss.2019.02.038, 240, 115-123, 2019.08, Background: Tumor immune reactions not only provide host defense but also accelerate tumor immune escape and phenotype switching. Here, we examined the association of programmed cell death ligand 1 (PD-L1) expression with epithelial-mesenchymal transition (EMT)–associated markers in pancreatic ductal adenocarcinoma (PDA) within the context of the tumor microenvironment. Materials and methods: PDA samples from 36 patients were analyzed for PD-L1, vimentin, E-cadherin, and Snail expressions and for PDA cell and immune cell infiltration. PD-L1 expression and EMT in PDA cell lines under conditions of altering interferon gamma (IFN-γ) signals were also assessed. Results: Immunohistochemistry revealed a significant correlation between vimentin and PD-L1 expression, whereas double staining showed them to be simultaneously expressed by PDA cells. Positive vimentin expression was associated with the infiltration of a lower number of CD8 + T cells and a higher number of FoxP3 + cells and poor patient prognosis (P = 0.03). PDA tumor cells promoted PD-L1 expression and EMT under the presence of IFN-γ which was inhibited by the signal transducer and activator of transcription (STAT)1 small interfering RNA. Conclusions: Strong correlations were observed between PD-L1 expression, EMT, and the immunosuppressive tumor microenvironment. Targeting STAT1 combined with PD-1/PD-L1 immunotherapy may improve outcomes for patients with PDA..
48. Xiaopeng Bai, Eikichi Ihara, Yoshihihro Otsuka, Shinichi Tsuruta, Katsuya Hirano, Yoshimasa Tanaka, Haruei Ogino, Mayumi Hirano, Takatoshi Chinen, Hirotada Akiho, Kazuhiko Nakamura, Yoshinao Oda, Yoshihiro Ogawa, Involvement of different receptor subtypes in prostaglandin E2-induced contraction and relaxation in the lower esophageal sphincter and esophageal body, European Journal of Pharmacology, 10.1016/j.ejphar.2019.172405, 857, 2019.08, Prostaglandin E2 (PGE2) plays a role in the pathogenesis of gastro-esophageal reflux disease (GERD). There are 4 subtypes of PGE2, PGE2 receptor 1, 2, 3 and 4 (EP 1–4). In GERD patents, PGE2, EP2 and EP4 are upregulated. However, the effects of PGE2 on esophageal motility remain elusive. We examined how PGE2 regulates motility in the porcine circular smooth muscle of the lower esophageal sphincter (LES), and the circular and longitudinal smooth muscle of the esophagus body in organ bath. PGE2 induced tonic relaxation in the LES and circular smooth muscle, but transient contraction in longitudinal smooth muscle. The relaxation of the LES and circular smooth muscle was similar in pattern and mechanism, but was much larger in the LES. The relaxation was completely blocked by a voltage-gated K+ channel blocker or 40 mM K+ depolarization, indicating the involvement of K+ channel. Longitudinal smooth muscle contraction was completely blocked by an L-type Ca2+ channel blocker, showing the contribution of Ca2+ movement. The involvement of the EP receptor in motility was examined with selective receptor agonists and antagonists. Activation of EP2 and EP4 caused relaxation in the LES and circular smooth muscle. Compatible with PGE2, EP2 and EP4 agonists caused more significant relaxation in the LES than in circular smooth muscle. EP1 contributed to the longitudinal smooth muscle contraction. The different effects of PGE2 in the LES, circular and longitudinal smooth muscle contributes to esophageal motility, their impairment might increase the amount and frequency of esophageal reflux..
49. Hitomi Mori, Makoto Kubo, Masaya Kai, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Tomofumi Osako, Reiki Nishimura, Nobuyuki Arima, Masayuki Okido, Junji Kishimoto, Yoshinao Oda, Masafumi Nakamura, T-bet+ lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer, Breast Cancer Research and Treatment, 10.1007/s10549-019-05256-2, 176, 3, 569-577, 2019.08, Purpose: T-box transcription factor 21 (T-bet), which is the master regulator of effector T-cell activation, is derived by stimulation of T-cell receptors. In this study, we focused on T-bet and examined the function of activated T cells. Methods: This study included 242 patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. The immunohistochemistry scoring for CD8 and T-bet expression on tumor-infiltrating lymphocytes (TILs) was defined as ≥ 30 per 6.25 × 10−3 mm2. Results: Of the 242 TNBC cases, CD8 was positively expressed in 127 (52.5%) tumors, and T-bet was positively expressed in 67 (27.7%) tumors. T-bet expression was significantly correlated with CD8 expression (p < 0.0001). Patients with T-bet+ tumors had longer overall survival (OS) compared with patients with T-bet tumors (p = 0.047). The combination of CD8+ and T-bet+ was associated with a better recurrence-free survival (RFS) and OS compared to CD8+/T-bet tumors (p = 0.037 and p = 0.024, respectively). Adjuvant chemotherapy provided significantly greater benefit to patients with T-bet+ tumors (p = 0.031 for RFS, p = 0.0003 for OS). Multivariate analysis revealed that T-bet expression on TILs was an independent and positive prognostic indicator (HR = 0.36, 95% confidence interval (CI) 0.12–0.94, p = 0.037 for RFS, HR = 0.30, 95% CI 0.07–0.95, p = 0.039 for OS). Conclusions: OS was significantly improved for patients with high T-bet-expressing TILs in TNBC. Thus, T-bet may be a predictive indicator for survival and various immunotherapy strategies in TNBC..
50. Masami Miki, Takamasa Oono, Nao Fujimori, Takehiro Takaoka, Ken Kawabe, Yoshihiro Miyasaka, Takao Ohtsuka, Daisuke Saito, Masafumi Nakamura, Yasuyuki Ohkawa, Yoshinao Oda, Mikita Suyama, Tetsuhide Ito, Yoshihiro Ogawa, CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors, Cancer Medicine, 10.1002/cam4.2232, 8, 8, 3748-3760, 2019.07, Although the postoperative recurrence rate for pancreatic neuroendocrine tumors (PNETs) is reported to be 13.5%-30%, the paucity of valuable biomarkers to predict recurrence poses a problem for the early detection of relapse. Hence, this study aimed to identify new biomarkers to predict the recurrence of PNETs. We performed RNA sequencing (RNA-Seq) on RNA isolated from frozen primary tumors sampled from all localized G1/G2 PNETs resected curatively from 1998 to 2015 in our institution. We calculated differentially expressed genes (DEGs) in tumor with and without recurrence (≥3 years) for the propensity-matched cohort. Gene ontology analysis for the identified DEGs was also performed. Furthermore, we evaluated the expression levels of candidate genes as recurrence predictors via immunostaining. Comparison of transcriptional levels in tumors with and without recurrence identified 166 DEGs. Up- and downregulated genes with high significance in these tumors were mainly related to extracellular organization and cell adhesion, respectively. We observed the top three upregulated genes, C-type lectin domain family 3 member A (CLEC3A), matrix metalloproteinase-7 (MMP7), and lipocalin2 (LCN2) immunohistochemically and compared their levels in recurrent and nonrecurrent tumors. Significantly higher recurrence rate was shown in patients with positive expression of CLEC3A (P = 0.028), MMP7 (P = 0.003), and LCN2 (P = 0.040) than that with negative expression. We identified CLEC3A, MMP7, and LCN2 known to be associated with the phosphatidylinositol-3-kinase/Akt pathway, as potential novel markers to predict the postoperative recurrence of PNETs..
51. Nakamura S, Sadakari Y, Ohtsuka T, Okayama T, Nakashima Y, Gotoh Y, Saeki K, Mori Y, Nakata K, Miyasaka Y, Onishi H, Oda Y, Goggins M, Nakamura M. , Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma., Ann Surg Oncol. , 26(7):2104-2111
, 2019.07.
52. Osoegawa T, Minoda Y, Ihara E, Komori K, Aso A, Goto A, Itaba S, Ogino H, Nakamura K, Harada N, Makihara K, Tsuruta S, Yamamoto H, Ogawa Y. , Mucosal incision assisted biopsy vs. endoscopic ultrasound-guided fine-needle aspiration with a rapid on-site evaluation for gastric subepithelial lesions: A randomized crossover study. , Dig Endosc. , 31(4):413-421, 2019.07.
53. Taichi Matsubara, Kazuki Takada, Koichi Azuma, Shinkichi Takamori, Gouji Toyokawa, Akira Haro, Atsushi Osoegawa, Tetsuzo Tagawa, Akihiko Kawahara, Jun Akiba, Isamu Okamoto, Yoichi Nakanishi, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara, A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma, Annals of Surgical Oncology, 10.1245/s10434-019-07257-3, 26, 6, 1925-1933, 2019.06, Background: Immunotherapy targeting programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has shown dramatic therapeutic effects for lung squamous cell carcinoma (SCC), and PD-L1 expression has been shown not only to be a predictive biomarker for response to immunotherapy but also a prognostic factor for lung SCC. However, the clinical significance of programmed death-ligand 2 (PD-L2), another PD-1 ligand, remains unclear. Therefore, we analyzed PD-L2 expression by immunohistochemistry in surgically resected primary lung SCC. Patients and Methods: PD-L1 and PD-L2 expression on tumor cells were analyzed in 211 primary lung SCC specimens by immunohistochemistry. Additionally, numbers of CD3 + , CD4 + , and CD8 + tumor-infiltrating lymphocytes were also examined. Results: The rates of positive PD-L2 expression were 77.3% and 67.3% using 5% and 10% cut-off values, respectively. Low PD-L2 expression on tumor cells was statistically associated with histological type (non-keratinizing/keratinizing) and lymphatic invasion. PD-L2-positive patients had significantly longer postoperative survival time (log-rank test; p = 0.0170 at 5% cut-off and p = 0.0500 at 10% cut-off). Furthermore, survival analysis according to PD-L1 and PD-L2 expression revealed that PD-L1-positive and PD-L2-negative patients had the most unfavorable prognosis. Conclusions: PD-L2 protein expression was associated with prognosis in primary lung SCC patients. PD-L2 expression might be a potential biomarker for response to PD-1/PD-L1-targeted immunotherapy, which should be investigated in future studies..
54. Kazuki Takada, Mototsugu Shimokawa, Kensuke Tanaka, Kenichi Kohashi, Akira Haro, Atsushi Osoegawa, Tetsuzo Tagawa, Koichi Azuma, Isamu Okamoto, Yoshinao Oda, Masaki Mori, Association between peripheral blood markers and immune-related factors on tumor cells in patients with resected primary lung adenocarcinoma, PloS one, 10.1371/journal.pone.0217991, 14, 6, 2019.06, We sought to identify peripheral blood markers associated with two immune-related factors —programmed cell death-ligand-2 (PD-L2) and indoleamine 2,3-dioxygenase-1 (IDO1)—that are expressed on tumor cells in primary lung adenocarcinoma (AD) specimens. We randomly selected 448 patients (70%) from 640 consecutive patients with resected stage I–III primary lung AD, who had been treated at that point with surgery alone. Expression of PD-L2 and IDO1 in these patients was assessed by immunohistochemistry, and evaluated with respect to peripheral blood markers measured before surgery, including white blood cells, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count (AMC), absolute eosinophil count (AEC), serum C-reactive protein, and serum lactate dehydrogenase levels. Membrane PD-L2 expression and cytoplasmic IDO1 expression were defined by tumor proportion score (TPS); samples with TPS < 1% were considered negative. Logistic regression models were used to identify variables associated with the immune-related factors. Advanced stage (P = 0.0090), higher AMC (P = 0.0195), and higher AEC (P = 0.0015) were independent predictors of IDO1 expression. PD-L2 expression was not associated with any tested peripheral blood markers. Peripheral blood markers, especially AMC and AEC, could potential predict IDO1 expression in lung AD. This study should be replicated in another cohort; further efforts to explore other biomarkers that predict PD-L2 or IDO1 expression are also warranted..
55. Shinichi Tsuruta, Yoshihiro Ohishi, Minako Fujiwara, Eikichi Ihara, Yoshihiro Ogawa, Eiji Oki, Masafumi Nakamura, Yoshinao Oda, Gastric hepatoid adenocarcinomas are a genetically heterogenous group; most tumors show chromosomal instability, but MSI tumors do exist, Human Pathology, 10.1016/j.humpath.2019.03.006, 88, 27-38, 2019.06, The Cancer Genome Atlas Research Network classified gastric adenocarcinoma into four molecular subtypes: (1) Epstein-Barr virus–positive (EBV), (2) microsatellite-instable (MSI), (3) chromosomal instable (CIN), and (4) genomically stable (GS). The molecular subtypes of gastric hepatoid adenocarcinomas are still largely unknown. We analyzed 52 hepatoid adenocarcinomas for the expression of surrogate markers of molecular subtypes (MLH1, p53, and EBER in situ hybridization) and some biomarkers (p21, p16, Rb, cyclin D1, cyclin E, β-catenin, Bcl-2, IMP3, ARID1A and HER2), and mutations of TP53, CTNNB1, KRAS, and BRAF. We analyzed 36 solid-type poorly differentiated adenocarcinomas as a control group. Hepatoid adenocarcinomas were categorized as follows: EBV group (EBER-positive), no cases (0%); MSI group (MLH1 loss), three cases (6%); “CIN or GS” (CIN/GS) group (EBER-negative, MLH1 retained), 49 cases (94%). In the CIN/GS group, most of the tumors (59%) had either p53 overexpression or TP53 mutation and a coexisting tubular intestinal-type adenocarcinoma component (90%), suggesting that most hepatoid adenocarcinomas should be categorized as a true CIN group. Hepatoid adenocarcinomas showed relatively frequent expressions of HER2 (score 3+/2+: 21%/19%). Hepatoid adenocarcinomas showed shorter survival, more frequent overexpressions of p16 (67%) and IMP3 (98%) than the control group. None of hepatoid adenocarcinomas had KRAS or CTNNB1 mutations except for one case each, and no hepatoid adenocarcinomas had BRAF mutation. In conclusion, gastric hepatoid adenocarcinomas are a genetically heterogenous group. Most hepatoid adenocarcinomas are “CIN,” but a small number of hepatoid adenocarcinomas with MSI do exist. Hepatoid adenocarcinomas are characterized by overexpressions of p16 and IMP3..
56. Shibui Y, Miyoshi K, Kohashi K, Kinoshita Y, Kuda M, Yamamoto H, Taguchi T, Oda Y, Glypican-3 expression in malignant small round cell tumors, Oncol Lett., 17(3):3523-3528, 2019.06.
57. Takamori S, Takada K, Azuma K, Jogo T, Shimokawa M, Toyokawa G, Hirai F, Tagawa T, Kawahara A, Akiba J, Okamoto I, Nakanishi Y, Oda Y, Hoshino T, Maehara Y. , Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients. , Ann Surg Oncol. , 26(6):1916-1924
, 2019.06.
58. Zilong Yan, Kenoki Ohuchida, Biao Zheng, Takashi Okumura, Shin Takesue, Hiromichi Nakayama, Chika Iwamoto, Koji Shindo, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Takao Ohtsuka, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura, CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis, Journal of Cancer Research and Clinical Oncology, 10.1007/s00432-019-02860-z, 145, 5, 1147-1164, 2019.05, Purpose: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer. Methods: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin–CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model. Results: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK–MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model. Conclusions: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis..
59. Ryota Souzaki, Naonori Kawakubo, Toshiharu Matsuura, Koichiro Yoshimaru, Yuhki Koga, Junkichi Takemoto, Yuichi Shibui, Kenichi Kohashi, Makoto Hayashida, Yoshinao Oda, Shouichi Ohga, Tomoaki Taguchi, Navigation surgery using indocyanine green fluorescent imaging for hepatoblastoma patients, Pediatric surgery international, 10.1007/s00383-019-04458-5, 35, 5, 551-557, 2019.05, Background: Technology for detecting liver tumors and identifying the bile ducts using indocyanine green (ICG) has recently been developed. However, the usefulness and limitations of ICG navigation surgery for hepatoblastoma (HB) have not been fully clarified. We herein report our experiences with surgical navigation using ICG for in HB patients. Methods: In 5 HB patients, 10 ICG navigation surgeries were performed using a 10-mm infrared fluorescence imaging scope after the injection of 0.5 mg/kg ICG intravenously. The surgical and clinical features were collected retrospectively. Results: Navigation surgery using ICG was performed for primary liver tumors in 4 cases, and the timing of ICG injection was 90.5 ± 33.7 h before the operation. All tumors exhibited intense fluorescence from the liver surface. ICG navigation for the primary liver tumor was useful for detecting the residual tumor at the stump and invasion to the diaphragm during surgery. Six lung surgeries using ICG navigation were performed. The timing of ICG injection was 21.8 ± 3.4 h before the operation. The size of the metastatic tumor was 7.4 ± 4.1 mm (1.2–15 mm). Of 11 metastatic tumors detected by computed tomography (CT), 10—including the smallest tumor (1.2 mm)—were able to be detected by ICG from the lung surface. The depth of the 10 ICG-positive tumors from the lung surface was 0.9 ± 1.9 mm (0–6 mm), and the depth of the single ICG-negative tumor was 12 mm. One lesion not detected by CT showed ICG false positivity. Conclusion: Navigation surgery using ICG for patients with HB was useful for identifying tumors and confirming complete resection. However, in ICG navigation surgery, we must be aware of the limitations with regard to the tumor size and the depth from the surface..
60. Takaki Akamine, Tetsuzo Tagawa, Kayo Ijichi, Gouji Toyokawa, Shinkichi Takamori, Fumihiko Hirai, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara, The Significance of CD44 Variant 9 in Resected Lung Adenocarcinoma
Correlation with Pathological Early-Stage and EGFR Mutation, Annals of Surgical Oncology, 10.1245/s10434-018-07137-2, 26, 5, 1544-1551, 2019.05, Background: CD44 isoforms serve as a marker for cancer stem cells. CD44 variant 9 (CD44v9) contributes to the defense against reactive oxygen species, resulting in resistance to chemoradiotherapy. However, the significance of CD44v9 in patients with lung adenocarcinoma is unknown. Methods: We used immunohistochemical analysis to retrospectively analyze CD44v9 expression in 268 surgically resected lung adenocarcinomas and investigated the association between CD44v9 expression and patients’ clinicopathological features. Results: The expression of CD44v9 in 193 of 268 (72.0%) patients was significantly associated with early-stage cancer, low-grade tumors, absence of vessel and pleural invasion, and a mutated epidermal growth factor receptor (EGFR) gene. Multivariate logistic analysis revealed that CD44v9 expression was significantly associated with early-stage disease [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.14–0.59; p < 0.001] and mutant EGFR (OR 2.53, 95% CI 1.06–6.04; p = 0.036). The percentage of CD44v9-positive tumors was higher in the earlier stages of disease; however, there was no significant difference in the survival of patients in each stage of disease who had positive or negative CD44v9 expression. Conclusion: CD44v9 was highly expressed in EGFR-mutant tumors, particularly in early-stage lung adenocarcinoma, suggesting that CD44v9 expression may play an important role in EGFR-mutant tumors..
61. Ito T, Takeda A, Fujiwara K, Hasegawa E, Nakao S, Ohishi Y, Oda Y, Yoshikawa H, Sonoda KH. , Risk factors for failure of vitrectomy cell block technique in cytological diagnosis of vitreoretinal lymphoma., Graefes Arch Clin Exp Ophthalmol. , 257(5):1029-1036, 2019.05.
62. Miyasaka Y, Ohtsuka T, Kimura R, Matsuda R, Mori Y, Nakata K, Kakihara D, Fujimori N, Ohno T, Oda Y, Nakamura M. , Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Borderline Resectable Pancreatic Cancer Potentially Improves Survival and Facilitates Surgery., Ann Surg Oncol. , 26(5):1528-1534, 2019.05.
63. Shinji Kohsaka, Kenji Tatsuno, Toshihide Ueno, Masaaki Nagano, Aya Shinozaki-Ushiku, Tetsuo Ushiku, Daiya Takai, Masachika Ikegami, Hiroshi Kobayashi, Hidenori Kage, Mizuo Ando, Keisuke Hata, Hiroki Ueda, Shogo Yamamoto, Shinya Kojima, Kumiko Oseto, Keisuke Akaike, Yoshiyuki Suehara, Takuo Hayashi, Tsuyoshi Saito, Fumiyuki Takahashi, Kazuhisa Takahashi, Kazuya Takamochi, Kenji Suzuki, Satoshi Nagayama, Yoshinao Oda, Koshi Mimori, Soichiro Ishihara, Yutaka Yatomi, Takahide Nagase, Jun Nakajima, Sakae Tanaka, Masashi Fukayama, Katsutoshi Oda, Masaomi Nangaku, Kohei Miyazono, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Comprehensive assay for the molecular profiling of cancer by target enrichment from formalin-fixed paraffin-embedded specimens, Cancer Science, 10.1111/cas.13968, 110, 4, 1464-1479, 2019.04, Tumor molecular profiling is becoming a standard of care for patients with cancer, but the optimal platform for cancer sequencing remains undetermined. We established a comprehensive assay, the Todai OncoPanel (TOP), which consists of DNA and RNA hybridization capture-based next-generation sequencing panels. A novel method for target enrichment, named the junction capture method, was developed for the RNA panel to accurately and cost-effectively detect 365 fusion genes as well as aberrantly spliced transcripts. The TOP RNA panel can also measure the expression profiles of an additional 109 genes. The TOP DNA panel was developed to detect single nucleotide variants and insertions/deletions for 464 genes, to calculate tumor mutation burden and microsatellite instability status, and to infer chromosomal copy number. Clinically relevant somatic mutations were identified in 32.2% (59/183) of patients by prospective TOP testing, signifying the clinical utility of TOP for providing personalized medicine to cancer patients..
64. Yoshitaka Gotoh, Takao Ohtsuka, So Nakamura, Koji Shindo, Kenoki Ohuchida, Yoshihiro Miyasaka, Yasuhisa Mori, Naoki Mochidome, Yoshinao Oda, Masafumi Nakamura, Genetic assessment of recurrent pancreatic high-risk lesions in the remnant pancreas
Metachronous multifocal lesion or local recurrence?, Surgery (United States), 10.1016/j.surg.2018.10.025, 165, 4, 767-774, 2019.04, Background: It is difficult to determine whether a second high-risk lesion, including pancreatic ductal adenocarcinoma or high-grade pancreatic intraepithelial neoplasm, is a metachronous multifocal lesion or represents local recurrence after resection of the first high-risk lesion. This study attempts to clarify the characteristics of second high-risk lesions in the remnant pancreas using genetic analyses. Methods: Clinicopathologic data were collected from 12 patients who underwent pancreatectomy for a second high-risk lesion in the remnant pancreas. We performed mutational and immunohistochemical analyses of 4 major genes—KRAS, TP53, CDKN2A, and SMAD4—associated with pancreatic ductal adenocarcinoma progression, as well as targeted next-generation sequencing. Results: Mutations in the four genes in the second high-risk lesion were consistent with the first lesion in four patients but were inconsistent in the remaining eight patients, and thus we considered that the latter eight patients likely had metachronous multifocal high-risk lesions and the other four patients had local recurrence. The estimated cumulative recurrence rate after resection of the second high-risk lesion was greater in the local recurrence group compared with the metachronous multifocal group, and the estimated cumulative disease-specific survival rate was greater in the metachronous multifocal group. Targeted next-generation sequencing demonstrated that the second lesions in the metachronous multifocal high-risk lesion group showed differences in founder mutations compared with the first lesion. In the local recurrence group, the founder mutations in the second lesion were common with those in the first lesion. Conclusion: Genetic assessment might help discriminate metachronous multifocal high-risk lesions from local recurrence..
65. Masayo Yoshimura, Yoshiaki Kinoshita, Makoto Hamasaki, Shinji Matsumoto, Tomoyuki Hida, Yoshinao Oda, Akinori Iwasaki, Kazuki Nabeshima, Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by immunohistochemistry, is useful for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia, Lung Cancer, 10.1016/j.lungcan.2019.02.004, 130, 187-193, 2019.04, Objective: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with poor prognosis. Loss of BRCA-associated protein 1 (BAP1) protein expression as detected by immunohistochemistry (IHC) and homozygous deletion (HD) of the 9p21 locus as detected by fluorescence in situ hybridization (FISH) permits differentiation of MPM from reactive mesothelial hyperplasia (RMH). We have previously reported that detecting the loss of methylthioadenosine phosphorylase (MTAP) using IHC is a surrogate assay for 9p21 FISH. Furthermore, enhancer of zeste homolog 2 (EZH2), which encodes a component of polycomb repressor complex 2 (PRC-2), has been overexpressed in various tumors as well as MPM. In the current study, we investigated whether EZH2 IHC assay, alone or in combination with BAP1 and MTAP IHC, is useful for distinguishing MPM from RMH. Materials and methods: We examined IHC expression of EZH2, BAP1, and MTAP, and 9p21 FISH in MPM (n = 38) and RMH (n = 29) and analyzed the sensitivity and specificity of each detection assay for distinguishing MPM from RMH. Results and conclusion: EZH2, BAP1, and MTAP IHC, and 9p21 FISH were characterized by a 100% specificity each and 44.7%, 52.6%, 47.4%, and 65.8% sensitivities, respectively. A combination of EZH2 and BAP1 IHC, and 9p21 FISH showed the greatest sensitivity (89.5%). Using IHC alone (EZH2, BAP1, and MTAP IHC) also yielded a good sensitivity of 86.9%; this level is high enough for routine diagnostics. There were no statistically significant associations between expression of EZH2 and that of other markers (BAP1 and MTAP IHC) or 9p21 HD. However, a high expression level of EZH2 was significantly associated with short survival (P = 0.025). In conclusion, adding a high expression level of EZH2 to a combination of BAP1 and MTAP loss, all detected by IHC, demonstrated useful for discriminating MPM from RMH..
66. Takashi Okumura, Kenoki Ouchida, Shin Kibe, Chika Iwamoto, Yohei Ando, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Masafumi Sada, Kohei Horioka, Naoki Mochidome, Makoto Arita, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Ohtsuka Takao, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura, Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix, International Journal of Cancer, 10.1002/ijc.31775, 144, 6, 1401-1413, 2019.03, Although recent studies revealed that adipose tissue accelerates pancreatic tumor progression with excessive extracellular matrix, key players for desmoplasia in the adipose microenvironment remains unknown. Here, we investigated the roles of adipose tissue-derived stromal cells (ASCs) in desmoplastic lesions and tumor progression by in vitro and in vivo experiments. In a three-dimensional (3-D) organotypic fat invasion model using visceral fat from CAG-EGFP mice, GFP-positive fibroblastic cells infiltrated toward cancer cells. When tumor cells were inoculated into transplanted visceral fat pads in vivo, tumor weights and stromal components were enhanced compared to subcutaneous and orthotopic tumor cells inoculated without fat pads. Expression of αSMA in established human ASCs was lower compared to cancer associated fibroblasts, and the 3-D collagen matrices produced by ASCs cultured in cancer cell-conditioned medium changed from loose to dense structures that affected the motility of cancer cells. Microarray analyses revealed upregulation of S100A4 in ASCs, while S100A4-positive stromal cells were observed at extrapancreatic invasion sites of human pancreatic cancer. The present findings indicate that ASCs are recruited to extrapancreatic invasion sites and produce dense collagen matrices that lead to enhanced tumor progression. Both inhibition of ASCs recruitment and activation could lead to a novel antistromal therapy..
67. Shin Kibe, Kenoki Ouchida, Yohei Ando, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Takashi Okumura, Chika Iwamoto, Koji Shindo, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Masaya Shimamoto, Ohtsuka Takao, Kazuhiro Mizumoto, Yoshinao Oda, Masafumi Nakamura, Cancer-associated acinar-to-ductal metaplasia within the invasive front of pancreatic cancer contributes to local invasion, Cancer Letters, 10.1016/j.canlet.2018.12.005, 444, 70-81, 2019.03, The pancreas is an organ prone to inflammation, fibrosis, and atrophy because of an abundance of acinar cells that produce digestive enzymes. A characteristic of pancreatic cancer is the presence of desmoplasia, inflammatory cell infiltration, and cancer-associated acinar atrophy (CAA) within the invasive front. CAA is characterized by a high frequency of small ducts and resembles acinar-to-ductal metaplasia (ADM). However, the clinical significance of changes in acinar morphology, such as ADM with acinar atrophy, within the tumor microenvironment remains unclear. Here, we find that ADM within the invasive front of tumors is associated with cell invasion and desmoplasia in an orthotopic mouse model of pancreatic cancer. An analysis of resected human tumors revealed that regions of cancer-associated ADM were positive for TGFα and that this TGFα expression was associated with primary tumor size and shorter survival times. Gene expression analysis identified distinct phenotypic profiles for cancer-associated ADM, sporadic ADM and chronic pancreatitis ADM. These findings suggest that the mechanisms driving ADM differ according to the specific tissue microenvironment and that cancer-associated ADM and acinar atrophy contribute to tumor cell invasion of the local pancreatic parenchyma..
68. Yuichi Shibui, Kina Miyoshi, Kenichi Kouhashi, Yoshiaki Kinoshita, Masaaki Kuda, Hidetaka Yamamoto, Tomoaki Taguchi, Yoshinao Oda, Glypican-3 expression in malignant small round cell tumors, Oncology Letters, 10.3892/ol.2019.9976, 17, 3, 3523-3528, 2019.03, Malignant small round cell tumors usually progress rapidly and show resistance to chemotherapy, and it is often difficult to make a definitive diagnosis based on their histological morphology. Glypican-3 (GPC3) is a highly tumor-specific antigen, and the overexpression of GPC3 was reported in many pediatric and adult malignancies. In the present study, we investigated the GPC3 expression in pediatric malignant small round cell tumors to assess its role in the differential diagnosis of the tumors. Immunohistochemistry was performed to assess the expression of GPC3 in samples from 84 rhabdomyosarcomas (RMSs; 44 alveolar and 40 embryonal RMSs), 62 Ewing sarcomas (EWSs), 35 neuroblastomas (NBs) and two desmoplastic small round cell tumors (DSRCTs). We performed a reverse transcription-quantitative polymerase chain reaction for GPC3 to determine the GPC3 mRNA expression in samples from 66 frozen tumors (23 RMSs, 28 EWSs and 15 NBs). The serum expression levels of GPC3 were analyzed in pre-operative blood samples from two RMS and eight NB patients. In total, 25% (21/84) of the RMSs and 3% (1/35) of the NBs exhibited a focal expression of GPC3, whereas, the other specimens showed no GPC3 expression. The GPC3 mRNA expression level of the RMSs with positive GPC3 expression (n=6) was significantly higher compared with the RMSs without such expression (n=17). A total of two cases of NB showed high serum levels of GPC3, but neither tumor showed immunoreactivity for GPC3. The immunohistochemical overexpression of GPC3 may be a candidate ancillary parameter in the differential diagnosis of RMS from EWS and DSRCT..
69. Junkichi Takemoto, Masaaki Kuda, Kenichi Kouhashi, Yuichi Yamada, Yutaka Koga, Izumi Kinoshita, Ryota Sozaki, Tomoaki Taguchi, Yoshinao Oda, HuC/D expression in small round cell tumors and neuroendocrine tumors
a useful tool for distinguishing neuroblastoma from childhood small round cell tumors, Human Pathology, 10.1016/j.humpath.2018.11.004, 85, 162-167, 2019.03, The RNA-binding protein HuC/D displays a neuron-specific expression and is involved in neuronal differentiation and the maintenance of the nervous system. Here we investigated the diagnostic value of HuC/D in neuroblastomas. We evaluated 85 neuroblastic tumors: 81 neuroblastomas; 3 ganglioneuroblastomas, intermixed; 1 ganglioneuroma, maturing; and 101 other tumors consisting of 34 Ewing sarcomas, 14 nephroblastomas, 11 rhabdomyosarcomas, 15 pulmonary small cell carcinomas, 18 pancreatic neuroendocrine tumors, and 9 pheochromocytomas. Immunohistochemistry for HuC/D, PHOX2B, and tyrosine hydroxylase was performed. The immunoreactivity for HuC/D was semiquantified using the total score (TS; range, 0-8). HuC/D positivity was defined as a TS ≥6. The TS of the neuroblastic tumors (mean TS, 7.94) was significantly higher than those of the other small round cell tumors and neuroendocrine tumors (P < .001) except for the pheochromocytomas (mean TS, 6.89; P = .074). HuC/D was positive in all 85 neuroblastic tumors, 1 (2.9%) Ewing sarcoma, 1 (6.7%) pulmonary small cell carcinoma, and 8 (89%) pheochromocytomas. PHOX2B was positive in all of the neuroblastic tumors and pheochromocytomas. Tyrosine hydroxylase was positive in 80 (94%) neuroblastic tumors, 1 (9.1%) rhabdomyosarcoma, and all of the pheochromocytomas. Therefore, HuC/D serves as a highly sensitive diagnostic marker to distinguish neuroblastomas from other small round cell tumors. The combination of HuC/D and PHOX2B staining may be valuable for the diagnosis of neuroblastic tumors, especially in the assessment of small sections. HuC/D expression in tumors may be related to catecholamine production or a neural crest–derived cell origin..
70. Yoshihiro Komohara, Hiroto Takeya, Nanako Wakigami, Natsuki Kusada, Hirofumi Bekki, Shin Ishihara, Motohiro Takeya, Yasuharu Nakashima, Yoshinao Oda, Positive correlation between the density of macrophages and T-cells in undifferentiated sarcoma, Medical Molecular Morphology, 10.1007/s00795-018-0201-3, 52, 1, 44-51, 2019.03, Undifferentiated sarcoma (US) is a frequent soft tissue sarcoma. Although the 10-year survival rate is around 60%, advanced US is highly resistant to chemo/radiotherapy. The tumor microenvironment (TME) is closely associated with tumor progression. However, few studies of infiltrated immune cells in US have been published. In this study, we evaluated tumor-associated macrophages (TAMs) and CD8-positive cytotoxic T lymphocytes (CTLs) in 28 cases of US. Iba1, CD163, and CD204 were used as markers for TAMs. The density of CTLs was positively correlated with the density of TAMs. However, a negative correlation was seen between the density of CTLs and the percentage of CD204-positive TAMs. We found no significant association between the density of Iba1-/CD204-/CD8-positive cells and clinicopathological factors. No significant correlation between immune cell infiltration and clinical outcome was observed. Although we found no significant association between immune cells and clinicopathological factors, these findings may provide new insight into the characterization of immune cells in the TME of US..
71. Yasuaki Hagio, Akira Shiraishi, masataka ishimura, Motoshi Sonoda, Katsuhide Eguchi, Hidetaka Yamamoto, Yoshinao Oda, Shoichi Ohga, Posttransplant recipient-derived CD4
+
T-cell lymphoproliferative disease in X-linked hyper-IgM syndrome, Pediatric Blood and Cancer, 10.1002/pbc.27529, 66, 3, 2019.03.
72. Yu Nakaji, Hiroshi Saeki, Kensuke Kudou, Ryota Nakanishi, Masahiko Sugiyama, Yuichiro Nakashima, Kouji Andou, Yoshinao Oda, Eiji Oki, Yoshihiko Maehara, Short- and long-term outcomes of surgical treatment for remnant gastric cancer after distal gastrectomy, Anticancer research, 10.21873/anticanres.13256, 39, 3, 1411-1415, 2019.03, Background/Aim: Remnant gastric cancer (RGC) after distal gastrectomy occurs in 1-2% of patients, while the biological features of RGC are unknown. Patients and Methods: A total of 22 consecutive patients with RGC who underwent total gastrectomy were analyzed. Their disease history included either gastric cancer (n=16) or peptic ulcer (n=6). Overall, 18 underwent open total gastrectomy (OTG) and 4 underwent laparoscopic total gastrectomy (LTG). Results: The mean number of lymph nodes dissected and metastatic lymph nodes was larger in the Ulcer group than in the Carcinoma group (p<0.005). The mean operation time was longer in the LTG than OTG (p<0.005). The median blood loss tended to be smaller in the LTG (p=0.090). Five-year overall and recurrence-free survival rates were 94% and 81%, respectively. Conclusion: The status of lymph node metastasis after surgery for RGC should be cautiously considered in the context of disease history. Both LTG and OTG can be treatment options for RGC..
73. Shinsuke Fujii, Kengo Nagata, Shinji Matsumoto, Ken ichi Kohashi, Akira Kikuchi, Yoshinao Oda, Tamotsu Kiyoshima, Naohisa Wada, Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development, Scientific reports, 10.1038/s41598-019-39686-1, 9, 1, 9(1):4257, 2019.03, Odontomas, developmental anomalies of tooth germ, frequently occur in familial adenomatous polyposis patients with activated Wnt/β-catenin signaling. However, roles of Wnt/β-catenin signaling in odontomas or odontogenic cells are unclear. Herein, we investigated β-catenin expression in odontomas and functions of Wnt/β-catenin signaling in tooth germ development. β-catenin frequently accumulated in nucleus and/or cellular cytoplasm of odontogenic epithelial cells in human odontoma specimens, immunohistochemically. Wnt/β-catenin signaling inhibited odontogenic epithelial cell proliferation in both cell line and tooth germ development, while inducing immature epithelial bud formation. We identified Semaphorin 3A (Sema3A) as a downstream molecule of Wnt/β-catenin signaling and showed that Wnt/β-catenin signaling-dependent reduction of Sema3A expression resulted in suppressed odontogenic epithelial cell proliferation. Sema3A expression is required in appropriate epithelial budding morphogenesis. These results suggest that Wnt/β-catenin signaling negatively regulates odontogenic epithelial cell proliferation and tooth germ development through decreased-Sema3A expression, and aberrant activation of Wnt/β-catenin signaling may associate with odontoma formation..
74. Takemoto J, Kuda M, Kohashi K, Yamada Y, Koga Y, Kinoshita I, Souzaki R, Taguchi T, Oda Y. , HuC/D expression in small round cell tumors and neuroendocrine tumors: a useful tool for distinguishing neuroblastoma from childhood small round cell tumors., Hum Pathol., 85:162-167, 2019.03.
75. Kibe S, Ohuchida K, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Koikawa K, Okumura T, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Shimamoto M, Ohtsuka T, Mizumoto K, Oda Y, Nakamura M. , Cancer-associated acinar-to-ductal metaplasia within the invasive front of pancreatic cancer contributes to local invasion., Cancer Lett., 444:70-81
, 2019.03.
76. Komohara Y, Takeya H, Wakigami N, Kusada N, Bekki H, Ishihara S, Takeya M, Nakashima Y, Oda Y. , Positive correlation between the density of macrophages and T-cells in undifferentiated sarcoma. , Med Mol Morphol. , 52(1):44-51, 2019.03.
77. Nakaji YU, Saeki H, Kudou K, Nakanishi R, Sugiyama M, Nakashima Y, Ando K, Oda Y, Oki E, Maehara Y. , Short- and Long-term Outcomes of Surgical Treatment for Remnant Gastric Cancer After Distal Gastrectomy., Anticancer Res. , 39(3):1411-1415, 2019.03.
78. Okumura T, Ohuchida K, Kibe S, Iwamoto C, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Koikawa K, Sada M, Horioka K, Mochidome N, Arita M, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M. , Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix. , Int J Cancer. , 144(6):1401-1413, 2019.03.
79. Takamori S, Toyokawa G, Shimokawa M, Kinoshita F, Kozuma Y, Matsubara T, Haratake N, Akamine T, Hirai F, Tagawa T, Oda Y, Maehara Y. , A novel prognostic marker in patients with non-small cell lung cancer: musculo-immuno-nutritional score calculated by controlling nutritional status and creatine kinase., J Thorac Dis. , 11(3):927-935
, 2019.03.
80. Gouji Toyokawa, Kazuki Takada, Tetsuzo Tagawa, Ryuji Hamamoto, Yuichi Yamada, Mototsugu Shimokawa, Yoshinao Oda, Yoshihiko Maehara, A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas, Annals of Thoracic Surgery, 10.1016/j.athoracsur.2018.08.056, 107, 2, 393-400, 2019.02, Background: Enhancer of zeste homolog 2 (EZH2) is reported to be involved in lung cancer pathogenesis via the epigenetic regulation of various genes. Recently, EZH2 was shown to control mechanisms of adaptive resistance to immunotherapy in melanoma; however, the association between EZH2 and programmed death-ligand 1 (PD-L1), which reflects the tumor microenvironment, remains poorly understood. Methods: A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression. Results: Among 428 patients, the EZH2 expression was identified in 219 (51.2%) patients, while the PD-L1 expression was observed in 88 (20.6%) patients. The recurrence-free and overall survival were significantly shorter in patients with the EZH2 expression than in those without it. A multivariate analysis showed that EZH2 remained an independent prognosticator for recurrence-free and overall survival. Patients with the EZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than did those without it. A logistic regression analysis with backward elimination revealed that the presence of lymphatic and vessel invasion and PD-L1 positivity were independently associated with the EZH2 expression, while age over 70 years, the presence of vessel invasion, wild-type epidermal growth factor receptor, and EZH2 positivity were significantly associated with the PD-L1 expression. Conclusions: EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequently than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma..
81. Satoshi Obata, Koichiro Yoshimaru, Kosuke Kirino, Tomoko Izaki, Satoshi Ieiri, Atsuyuki Yamataka, Tsugumichi Koshinaga, Jun Iwai, Hitoshi Ikeda, Hiroshi Matsufuji, Yoshinao Oda, Tomoaki Taguchi, Acquired isolated hypoganglionosis as a distinct entity
results from a nationwide survey, Pediatric surgery international, 10.1007/s00383-018-4398-y, 35, 2, 215-220, 2019.02, Purpose: Acquired isolated hypoganglionosis (A-IH) is a late-onset intestinal pseudo-obstruction disorder and shows different pathophysiological findings from congenital isolated hypoganglionosis (C-IH). In this study, we retrospectively examined five cases of A-IH and investigated the features of A-IH. Methods: Five cases of A-IH were extracted from a nationwide retrospective cohort study in 10 years, from which totally 355 cases of Allied Disorders of Hirschsprung’s Disease (ADHD) were collected. Results: Ages of onset were between 13 and 17 years in three cases, and 4 years and 4 months in ones. Initial symptoms were abdominal distension and/or chronic constipation in 4 cases, whereas one exhibited intestinal perforation. Affected lesions varied from case to case, extending various length of intestinal tracts. All cases underwent multiple operations (average: 4.6 times), such as enterostomy, resection of dilated intestines, and/or pull-through. Pathological findings showed the decreased numbers of ganglion cells and degeneration of ganglion cells, whereas the size of the plexus was normal. Currently, all cases were alive and almost all eat regular food without requiring parenteral feeding. Conclusion: A-IH is rare, but distinct entity characterized by different clinical courses and pathological findings from those of C-IH. The outcome is considered to be favorable after a resection of affected intestine..
82. Kazuki Takada, Kenichi Kouhashi, Mototsugu Shimokawa, Akira Haro, Atsushi Osoegawa, Tetsuzo Tagawa, Takashi Seto, Yoshinao Oda, Yoshihiko Maehara, Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma
Potential targets of novel combination therapy, Lung Cancer, 10.1016/j.lungcan.2018.12.008, 128, 26-32, 2019.02, Objectives: Combination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC). Materials and methods: The expression levels of IDO1, PD-L1, Ki-67, cluster of differentiation 3 (CD3), CD4, and CD8 in 202 patients with surgically resected primary lung SCC were evaluated by immunohistochemistry. Results: Among 202 patients, 176 (87.1%) were positive for IDO1 expression, 106 (52.5%) were positive for PD-L1 expression, and 99 (49.0%) showed co-expression of IDO1/PD-L1 proteins. Fisher's exact test showed a significant association between IDO1 and PD-L1 tumor proportion scores (P = 0.0011). Kaplan–Meier curve showed that PD-L1 alone and co-expression of IDO1 and PD-L1 were significantly associated with shorter overall survival, but IDO1 alone was not (log rank test: P = 0.0122, P = 0.0303 and P = 0.5168, respectively). The Ki-67 labeling index was significantly higher in patients with co-expression of IDO1 and PD-L1 than in patients without co-expression (Student's t-test: P = 0.0005). Moreover, IDO1/PD-L1 co-expression was significantly associated with high CD3, CD4, and CD8 expression (Fisher's exact test: P = 0.0033, P = 0.0003, and P < 0.0001, respectively). Conclusions: IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC..
83. Hirakawa N, Kuga H, Hirano Y, Sato J, Oribe N, Nakamura I, Hirano S, Ueno T, Oda Y, Togao O, Hiwatashi A, Honda H, Kanba S, Onitsuka T. , Neuroanatomical substrate of chronic psychosis in epilepsy: an MRI study., Brain Imaging Behav. , 2019.02.
84. Obata S, Yoshimaru K, Kirino K, Izaki T, Ieiri S, Yamataka A, Koshinaga T, Iwai J,Ikeda H, Matsufuji H, Oda Y, Taguchi T. , Acquired isolated hypoganglionosis as a distinct entity: results from a nationwide survey., Pediatr Surg Int., 35(2):215-220, 2019.02.
85. Takada K, Kohashi K, Shimokawa M, Haro A, Osoegawa A, Tagawa T, Seto T, Oda Y, Maehara Y. , Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma: Potential targets of novel combination therapy. , Lung Cancer. , 128:26-32
, 2019.02.
86. Toyokawa G, Takada K, Tagawa T, Hamamoto R, Yamada Y, Shimokawa M, Oda Y, Maehara Y. , A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas. , Ann Thorac Surg. , 107(2):393-400
, 2019.02.
87. Yohei Mano, Sachiyo Yoshio, Hirotaka Shoji, Shimagaki Tomonari, Yoshihiko Aoki, Nobuyoshi Aoyanagi, Toru Okamoto, Yoshiharu Matsuura, Yosuke Osawa, Kiminori Kimura, Kyohei Yugawa, Huanlin Wang, Yoshinao Oda, Tomoharu Yoshizumi, Yoshihiko Maehara, Tatsuya Kanto, Bone morphogenetic protein 4 provides cancer-supportive phenotypes to liver fibroblasts in patients with hepatocellular carcinoma, Journal of gastroenterology, 10.1007/s00535-019-01579-5, 2019.01, Background: Cancer-associated fibroblasts (CAFs) are essential constituents of cancer-supportive microenvironments. The high incidence of hepatocellular carcinoma (HCC) in advanced fibrosis patients implies that fibroblasts have a promoting effect on HCC development. We aimed to explore the regulators of phenotypes and function of CAFs in the liver. Methods: We established primary cancer-associated fibroblasts (CAFs) and non-cancerous liver fibroblasts (NFs) from 15 patients who underwent HCC resection. We compared phenotypes, capacity of cytokine/chemokine production and gene expression profiles between pairs of CAFs and NFs from the same donors. We examined resected tissue from additional 50 patients with HCC for immunohistochemical analyses. Results: The CAFs expressed more ACTA2 and COL1A1 than the NFs, suggesting that CAFs are more activated phenotype. The CAFs produced larger amounts of IL-6, IL-8 and CCL2 than the NFs, which led to invasiveness of HuH7 in vitro. We found that Bone Morphogenetic Protein-4 (BMP4) is up-regulated in CAFs compared to NFs. The CAF phenotype and function were gained by BMP4 over-expression or recombinant BMP4 given to fibroblasts, all of which decreased with BMP4 knockdown. In tissues obtained from the patients, BMP4-positive cells are mainly observed in encapsulated fibrous lesions and HCC. Positive expression of BMP4 in HCC in resected tissues, not in fibroblasts, was associated with poorer postoperative overall survival in patients with HCC. Conclusion: Endogenous and exogenous BMP4 activate liver fibroblasts to gain capacity of secreting cytokines and enhancing invasiveness of cancer cells in the liver. BMP4 is one of the regulatory factors of CAFs functioning in the microenvironment of HCC..
88. Yohei Nakashima, Ohtsuka Takao, So Nakamura, Yasuhisa Mori, Kohei Nakata, Yoshihiro Miyasaka, Kosei Ishigami, Ryota Matsuda, Yoshinao Oda, Masafumi Nakamura, Clinicopathological characteristics of non-functioning cystic pancreatic neuroendocrine tumors, Pancreatology, 10.1016/j.pan.2018.11.010, 19, 1, 50-56, 2019.01, Background/objectives: The biological features of cystic pancreatic neuroendocrine tumors (PNETs) remain unclear. The aim of this study was to clarify the clinicopathological characteristics of non-functioning PNETs (NF-PNETs) with a cystic component. Methods: The medical records of 75 patients with NF-PNETs who had undergone resection in our institution were retrospectively reviewed. Clinicopathological factors were compared between PNETs with and without a cystic component. Expression of somatostatin 2 receptor (SSTR-2) was also analyzed. Results: Cystic PNETs were diagnosed in 14 patients (19%). The proportion of men was significantly higher for cystic than solid PNETs (79% vs. 44%, P < 0.05) and cystic PNETs were significantly larger than solid PNETs (25 mm vs. 17 mm, P < 0.01). However, there were no significant differences in the prevalence of lymph node metastases (14% vs. 10%, P = 0.64), hepatic metastasis (7% vs. 3%, P = 0.54), or disease-free survival rate (both 86%, P = 0.29) between PNETs with and without a cystic component. SSTR-2 expression was more frequently observed in PNETs with a cystic component than in those without (100% vs. 70%, P < 0.01). Conclusions: Although cystic PNETs were larger upon diagnosis than solid PNETs in this study, prognosis after surgical resection did not differ significantly between these types of PNET. Somatostatin receptor scintigraphy and somatostatin analogues may be more useful for diagnosing and treating cystic PNETs, respectively..
89. Yoshihiro Miyasaka, Ohtsuka Takao, Ryuichiro Kimura, Ryota Matsuda, Yasuhisa Mori, Kohei Nakata, Daisuke Kakihara, Nao Fujimori, Takamasa Ohno, Yoshinao Oda, Masafumi Nakamura, Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Borderline Resectable Pancreatic Cancer Potentially Improves Survival and Facilitates Surgery, Annals of Surgical Oncology, 10.1245/s10434-019-07309-8, 2019.01, Background: Accumulation of evidence suggests that neoadjuvant chemotherapy improves the outcomes of borderline resectable pancreatic cancer (BRPC). Gemcitabine plus nab-paclitaxel (GnP) has been widely accepted as systemic chemotherapy for unresectable pancreatic cancer and reportedly results in remarkable tumor shrinkage. This study was performed to evaluate the safety and efficacy of neoadjuvant chemotherapy using neoadjuvant GnP for BRPC. Methods: The medical records of 57 patients who underwent treatment of BRPC from 2010 to 2017 were retrospectively reviewed. The patient characteristics and short- and intermediate-term outcomes were compared between the GnP and upfront surgery (UFS) groups. Results: The GnP group comprised 31 patients and the UFS group comprised 26 patients. The patient characteristics were comparable with the exception of a higher prevalence of arterial involvement in the GnP group. Twenty-seven of the 31 patients (87%) in the GnP group and all 26 patients in the UFS group underwent resection. The GnP group showed a significantly shorter operation time (429 vs. 509.5 min, p = 0.0068), less blood loss (760 vs. 1324 ml, p = 0.0115), and a higher R0 resection rate (100% vs. 77%, p = 0.0100) than the UFS group. Postoperative complications and hospital stay were comparable between the two groups, and no treatment-related mortality occurred in either group. Both the disease-free survival and overall survival times were significantly longer in the GnP group (p = 0.0018 and p = 0.0024, respectively). Conclusions: Neoadjuvant GnP is a safe and effective treatment strategy for BRPC. It potentially improves patients’ prognosis and facilitates surgical procedures..
90. So Nakamura, Yoshihiko Sadakari, Ohtsuka Takao, Takafumi Okayama, Yohei Nakashima, Yoshitaka Gotoh, Kiyoshi Saeki, Yasuhisa Mori, Kohei Nakata, Yoshihiro Miyasaka, Hideya Ohnishi, Yoshinao Oda, Michael Goggins, Masafumi Nakamura, Pancreatic Juice Exosomal MicroRNAs as Biomarkers for Detection of Pancreatic Ductal Adenocarcinoma, Annals of Surgical Oncology, 10.1245/s10434-019-07269-z, 2019.01, Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. Several studies have recently suggested that exosomes may have potential as novel biomarkers. This study aimed to isolate exosomes from pancreatic juice and to investigate whether exosomal microRNAs (ex-miRs) could be used as biomarkers for PDAC. Methods: Pancreatic juice was collected from patients with PDAC and chronic pancreatitis (CP) by endoscopic retrograde pancreatography. Exosomes were extracted by ultracentrifugation. The presence of exosomes was confirmed by electron microscopy and Western blotting using anti-CD63, -CD81, and -TSG101 antibodies. Relative levels of ex-miR-21 and ex-miR-155 were quantified and compared between PDAC and CP patients. Results: A total of 35 pancreatic juice samples (27 PDAC and 8 CP) were collected. Relative levels of both ex-miR-21 and ex-miR-155 were significantly higher in PDAC patients compared with CP patients (p < 0.001 and p = 0.008, respectively). By contrast, no significant difference was apparent in relative levels of miR-21 and miR-155 in whole pancreatic juice from PDAC patients compared with CP patients (p = 0.08 and p = 0.61, respectively). Ex-miR-21 and ex-miR-155 levels discriminated PDAC patients from CP patients with area under the curve values of 0.90 and 0.89, respectively. The accuracies of ex-miR-21 levels, ex-miR-155 levels, and pancreatic juice cytology were 83%, 89%, and 74%, respectively. When combining the results of ex-miR profiling with pancreatic juice cytology, the accuracy was improved to 91%. Conclusions: We successfully extracted exosomes from pancreatic juice. Ex-miRs, including ex-miR-21 and ex-miR-155, in pancreatic juice may be developed as biomarkers for PDAC..
91. Shinkichi Takamori, Kazuki Takada, Koichi Azuma, Tomoko Jogo, Mototsugu Shimokawa, Gouji Toyokawa, Fumihiko Hirai, Tetsuzo Tagawa, Akihiko Kawahara, Jun Akiba, Isamu Okamoto, Yoichi Nakanishi, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara, Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients, Annals of Surgical Oncology, 10.1245/s10434-019-07231-z, 2019.01, Background: Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. Methods: The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival. Results: Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018). Conclusions: The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies..
92. Takako Ito, Atsunobu Takeda, Kohta Fujiwara, Eiichi Hasegawa, shintaro nakao, Yoshihiro Ohishi, Yoshinao Oda, Hiroshi Yoshikawa, Kohei Sonoda, Risk factors for failure of vitrectomy cell block technique in cytological diagnosis of vitreoretinal lymphoma, Graefe's Archive for Clinical and Experimental Ophthalmology, 10.1007/s00417-019-04266-6, 2019.01, Purpose: To determine the factors that may affect the accuracy of vitrectomy cell block technique in detecting atypical lymphoid cells in patients with vitreoretinal lymphoma (VRL). Methods: We retrospectively reviewed 43 eyes in 39 patients who underwent vitrectomy for definitive histological diagnosis of VRL with vitrectomy cell block technique and/or smear preparation at Kyushu University Hospital from January 2001 to March 2016. The association of detection of atypical lymphoid cells using vitrectomy cell block technique with the following factors was assessed using logistic regression analysis: age at diagnosis, sex, presence or absence of concurrent cataract surgery with vitrectomy, clinical grading of vitreous haze, presence or absence of subretinal tumor infiltration, interval between initial symptoms and vitrectomy, and presence or absence of systemic corticosteroid therapy before vitrectomy. Results: Atypical lymphoid cells were more significantly detected using vitrectomy cell block technique compared to that using smear preparation (p = 0.018). After adjusting for age and sex, concurrent cataract surgery (odds ratio [OR], 10.41; 95% confidence interval [CI], 1.42–76.41) and subretinal tumor infiltration (OR, 5.06; 95% CI, 1.06–24.32) were significantly associated with failure of histological analysis with vitrectomy cell blocks. In multivariable logistic regression analysis, similar results were obtained, although subretinal tumor infiltration was only marginally associated with the detective capability of the technique. Conclusion: Vitrectomy cell block technique significantly improved the definitive diagnosis of VRL. Concurrent cataract surgery with vitrectomy and subretinal tumor infiltration were risk factors for failure in vitrectomy cell blocks..
93. Keishi Komori, Eikichi Ihara, Yosuke Minoda, Haruei Ogino, Taisuke Sasaki, Minako Fujiwara, Yoshinao Oda, Yoshihiro Ogawa, The Altered Mucosal Barrier Function in the Duodenum Plays a Role in the Pathogenesis of Functional Dyspepsia, Digestive Diseases and Sciences, 10.1007/s10620-019-5470-8, 2019.01, Background: An altered gastrointestinal barrier function is reportedly associated with the pathogenesis of functional dyspepsia (FD); however, the pathogenesis of FD has not yet been fully elucidated. Aims: The objective of the present study was to determine whether the mucosal barrier function is impaired in patients with FD and to investigate the mechanisms underlying FD. Methods: The present study included patients with FD (FD group, n = 24), non-FD patients with abdominal symptoms (symptomatic control group, n = 14), and patients with no abdominal symptoms (asymptomatic control group, n = 20). The groups were compared regarding the mucosal electrical impedance (MI) values of the stomach and duodenum, which were measured using a tissue conductance meter during esophagogastroduodenoscopy. Results: There were no significant differences between the three groups in the MI of the stomach. In contrast, the duodenal MI of the FD group (17.8 ± 4.3 Ω) was significantly lower than those of the symptomatic control group (27.2 ± 6.4 Ω, p < 0.0001) and asymptomatic control group (23.0 ± 7.4 Ω, p = 0.016). The expression of zonula occludens-1 (ZO-1) was significantly lower in the FD group than in the symptomatic control group (p = 0.011), where ZO-1 was positively correlated with the duodenal MI (β = 0.513, p = 0.017). The interleukin (IL)-1β expression was significantly higher in the FD group than in the symptomatic control group (p = 0.041), where IL-1β was inversely correlated with the duodenal MI (β = − 0.600, p = 0.004). Conclusions: The mucosal barrier function of the duodenum was altered in patients with FD. Both a decreased ZO-1 and increased IL-1β may play a role in the pathogenesis of FD..
94. Fumihiko Kinoshita, Kazuki Takada, Yuichi Yamada, Yuka Oku, Keisuke Kosai, Yuki Ono, Kensuke Tanaka, Sho Wakasu, Taro Oba, Atsushi Osoegawa, Tetsuzo Tagawa, Mototsugu Shimokawa, Yoshinao Oda, Masaki Mori, Combined Evaluation of Tumor-Infiltrating CD8 + and FoxP3 + Lymphocytes Provides Accurate Prognosis in Stage IA Lung Adenocarcinoma, Annals of Surgical Oncology, 10.1245/s10434-019-08029-9, 2019.01, Background: Immunotherapy has become a standard treatment option for non-small cell lung cancer (NSCLC), with the tumor microenvironment attracting significant attention. CD8 + and forkhead box protein P3 + (FoxP3 +) tumor-infiltrating lymphocytes (TILs) influence the tumor microenvironment, but the clinical significance of CD8 + and FoxP3 + TILs in stage IA lung adenocarcinoma (LAD) is poorly understood. Methods: We analyzed 203 patients with stage IA primary LAD who had undergone surgery at Kyushu University from January 2003 to December 2012. We evaluated CD8 + and FoxP3 + TILs by immunohistochemistry. We set the cutoff values at 50 cells/0.04 mm2 for CD8 + TILs and 20 cells/0.04 mm2 for FoxP3 + TILs, respectively. We divided the patients into four groups: CD8-Low/FoxP3-Low; CD8-High/FoxP3-Low; CD8-Low/FoxP3-High; and CD8-High/FoxP3-High. We compared clinical outcomes among them. Programmed cell death ligand-1 (PD-L1) expression by tumor cells was also evaluated as previously reported. Results: Respectively, 104 (51.2%), 46 (22.7%), 22 (10.8%), and 31 (15.3%) patients were classified as CD8-Low/FoxP3-Low, CD8-High/FoxP3-Low, CD8-Low/FoxP3-High, and CD8-High/FoxP3-High. Both disease-free survival (DFS) and overall survival (OS) were significantly worse in the CD8-Low/FoxP3-High group than the other groups (5-year DFS: 66.3% vs. 90.5%; P = 0.0007, 5-year OS: 90.9% vs. 97.0%; P = 0.0077). In the multivariate analysis, CD8-Low/FoxP3-High and PD-L1 expression were independent prognostic factors of DFS, and lymphatic invasion, surgical procedure, and PD-L1 expression were independent prognostic factors of OS. Conclusions: CD8-Low/FoxP3-High was an independent prognostic factor of DFS (hazard ratio: 3.22; 95% confidence interval: 1.321–7.179; P = 0.0121) in stage IA LAD. Immunosuppressive conditions were associated with poor prognosis in stage IA LAD..
95. Takafumi Hiramoto, Maino Tahara, Jiyuan Liao, Yasushi Soda, Yoshie Miura, Ryo Kurita, Hiroshi Hamana, Kota Inoue, Hiroshi Kohara, Shohei Miyamoto, Yasuki Hijikata, Shinji Okano, Yoshiyuki Yamaguchi, Yoshinao Oda, Kenji Ichiyanagi, Hidehiro Toh, Hiroyuki Sasaki, Hiroyuki Kishi, Akihide Ryo, Atsushi Muraguchi, Makoto Takeda, Kenzaburo Tani, Non-transmissible MV Vector with Segmented RNA Genome Establishes Different Types of iPSCs from Hematopoietic Cells, Molecular Therapy, 10.1016/j.ymthe.2019.09.007, 2019.01, Recent advances in gene therapy technologies have enabled the treatment of congenital disorders and cancers and facilitated the development of innovative methods, including induced pluripotent stem cell (iPSC) production and genome editing. We recently developed a novel non-transmissible and non-integrating measles virus (MV) vector capable of transferring multiple genes simultaneously into a wide range of cells through the CD46 and CD150 receptors. The MV vector expresses four genes for iPSC generation and the GFP gene for a period of time sufficient to establish iPSCs from human fibroblasts as well as peripheral blood T cells. The transgenes were expressed differentially depending on their gene order in the vector. Human hematopoietic stem/progenitor cells were directly and efficiently reprogrammed to naive-like cells that could proliferate and differentiate into primed iPSCs by the same method used to establish primed iPSCs from other cell types. The novel MV vector has several advantages for establishing iPSCs and potential future applications in gene therapy. This new non-transmissible and non-integrating measles virus vector, which can transfer multiple genes simultaneously into a wide range of cells through the CD46 and CD150 receptors and induce primed or naive-like pluripotent stem cells from hematopoietic cells in the same condition, will definitely contribute to the gene and cell therapy..
96. Ryo Koba, Hayato Fujita, Maiko Nishibori, Kiyoshi Saeki, Kinuko Nagayoshi, Yoshihiko Sadakari, Shuntaro Nagai, Oki Sekizawa, Kiyofumi Nitta, Tatsuya Manabe, Takashi Ueki, Tatsuhiro Ishida, Yoshinao Oda, Masafumi Nakamura, Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer
In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry, International Journal of Cancer, 10.1002/ijc.32592, 2019.01, Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85–11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04–196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum..
97. Keisuke Kodama, Kenzo Sonoda, Masako Kijima, Shinichiro Yamaguchi, Hiroshi Yagi, Masafumi Yasunaga, Tatsuhiro Ohgami, Ichiro Onoyama, Eisuke Kaneki, Kaoru Okugawa, Hideaki Yahata, Yoshihiro Ohishi, Yoshinao Oda, Kiyoko Kato, Retrospective analysis of treatment and prognosis for uterine leiomyosarcoma
10-year experience of a single institute, Asia-Pacific Journal of Clinical Oncology, 10.1111/ajco.13286, 2019.01, Aim: Uterine leiomyosarcoma (ULMS) is a highly aggressive and lethal disease. This malignancy remains the most common type of uterine sarcoma, affecting approximately 0.4/100 000 women each year. Our aim was to assess the treatment and prognosis of ULMS patients. Methods: A total of 14 patients were treated at our institution between January 2008 and July 2017. We retrospectively analyzed their clinicopathological variables, treatment and prognosis. Results: The median patient age was 63 years (range, 35–83 years). The largest group of patients had stage IB disease (stage IB, n = 8; IIB, n = 2; IIIB, n = 1; IVB, n = 3) and the largest group by histological subtype was ordinary (ordinary, n = 11; myxoid, n = 2; epithelioid, n = 1). Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed for all patients, with additional surgical procedures (e.g., tumor resection, lymphadenectomy) performed if necessary. Twelve patients received adjuvant chemotherapy (ACT) consisting of gemcitabine and docetaxel. Ten patients experienced recurrence and received multidisciplinary therapies, including tumor resection, chemotherapy, radiation and targeted therapies. The median observation period was 17 months (range, 5–75 months), and 11 patients were alive (without disease, n = 5; with disease, n = 6). Intriguingly, five of eight stage IB patients who received postoperative ACT were alive without disease. Conclusion: ULMS is rare but is associated with a poor prognosis, even if multidisciplinary therapies are administered. However, ACT appears to be effective in improving the prognosis of patients with stage IB disease..
98. Olca Basturk, Britta Weigelt, Volkan Adsay, Jamal K. Benhamida, Gokce Askan, Lu Wang, Maria E. Arcila, Giuseppe Zamboni, Noriyoshi Fukushima, Rodrigo Gularte-Mérida, Arnaud Da Cruz Paula, Pier Selenica, Rahul Kumar, Fresia Pareja, Christopher A. Maher, John Scholes, Yoshinao Oda, Donatella Santini, Leona A. Doyle, Iver Petersen, Uta Flucke, Christian Koelsche, Samuel J. Reynolds, Aslihan Yavas, Andreas von Deimling, Jorge S. Reis-Filho, David S. Klimstra, Sclerosing epithelioid mesenchymal neoplasm of the pancreas – a proposed new entity, Modern Pathology, 10.1038/s41379-019-0334-5, 2019.01, We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We aimed to define their clinicopathologic features and whether they are characterized by recurrent molecular signatures. Eight cases were identified; studied histologically and by immunohistochemistry. Selected cases were also subjected to whole-exome sequencing (WES; n = 4), RNA-sequencing (n = 6), Archer FusionPlex assay (n = 5), methylation profiling using the Illumina MethylationEPIC (850k) array platform (n = 6), and TERT promoter sequencing (n = 5). Six neoplasms occurred in females. The mean age was 43 years (range: 26–75). Five occurred in the head/neck of the pancreas. All patients were treated surgically; none received neoadjuvant/adjuvant therapy. All patients are free of disease after 53 months of median follow-up (range: 8–94). The tumors were well-circumscribed, and the median size was 1.8 cm (range: 1.3–5.8). Microscopically, the unencapsulated tumors had a geographic pattern of epithelioid cell nests alternating with spindle cell fascicles. Some areas showed dense fibrosis, in which enmeshed tumor cells imparted a slit-like pattern. The predominant epithelioid cells had scant cytoplasm and round-oval nuclei with open chromatin. The spindle cells displayed irregular, hyperchromatic nuclei. Mitoses were rare. No lymph node metastases were identified. All tumors were positive for vimentin, CD99 and cytokeratin (patchy), while negative for markers of solid pseudopapillary neoplasm, neuroendocrine, acinar, myogenic/rhabdoid, vascular, melanocytic, or lymphoid differentiation, gastrointestinal stromal tumor as well as MUC4. Whole-exome sequencing revealed no recurrent somatic mutations or amplifications/homozygous deletions in any known oncogenes or tumor suppressor genes. RNA-sequencing and the Archer FusionPlex assay did not detect any recurrent likely pathogenic gene fusions. Single sample gene set enrichment analysis revealed that these tumors display a likely mesenchymal transcriptomic program. Unsupervised analysis (t-SNE) of their methylation profiles against a set of different mesenchymal neoplasms demonstrated a distinct methylation pattern. Here, we describe pancreatic neoplasms with unique morphologic/immunophenotypic features and a distinct methylation pattern, along with a lack of abnormalities in any of key genetic drivers, supporting that these neoplasms represent a novel entity with an indolent clinical course. Given their mesenchymal transcriptomic features, we propose the designation of “sclerosing epithelioid mesenchymal neoplasm” of the pancreas..
99. Sei Shu, Makoto Iimori, Takeshi Wakasa, Koji Ando, Hiroshi Saeki, Yoshinao Oda, Eiji Oki, Yoshihiko Maehara, The balance of forces generated by kinesins controls spindle polarity and chromosomal heterogeneity in tetraploid cells, Journal of cell science, 10.1242/jcs.231530, 132, 24, 2019.01, Chromosomal instability, one of the most prominent features of tumour cells, causes aneuploidy. Tetraploidy is thought to be an intermediate on the path to aneuploidy, but the mechanistic relationship between the two states is poorly understood. Here, we show that spindle polarity (e.g. bipolarity or multipolarity) in tetraploid cells depends on the level of functional phosphorylated Eg5, a mitotic kinesin, localised to the spindle. Multipolar spindles are formed in cells with high levels of phosphorylated Eg5. This process is suppressed by inhibition of Eg5 or expression of a non-phosphorylatable Eg5 mutant, as well as by changing the balance between opposing forces required for centrosome separation. Tetraploid cells with high levels of functional Eg5 give rise to a heterogeneous aneuploid population through multipolar division, whereas cells with low levels of functional Eg5 continue to undergo bipolar division and remain tetraploid. Furthermore, Eg5 protein levels correlate with ploidy status in tumour specimens. We provide a novel explanation for the tetraploid intermediate model, i.e. spindle polarity and subsequent tetraploid cell behaviour are determined by the balance of forces generated by mitotic kinesins at the spindle..
100. Nakashima Y, Ohtsuka T, Nakamura S, Mori Y, Nakata K, Miyasaka Y, Ishigami K, Matsuda R, Oda Y, Nakamura M. , Clinicopathological characteristics of non-functioning cystic pancreatic neuroendocrine tumors., Pancreatology. , 19(1):50-56, 2019.01.
101. Huanlin Wang, Tomoharu Yoshizumi, Shinji Itoh, Toru Ikegami, Noboru Harada, Yoshinao Oda, Masaki Mori, Retroperitoneal schwannoma preoperatively diagnosed as liver metastasis from colon cancer
A case report, International Journal of Surgery Case Reports, 10.1016/j.ijscr.2019.09.031, 64, 31-34, 2019, Background: Retroperitoneal schwannomas are rare. Case presentation: We here report a case of 64-year-old woman who was referred to her local hospital for abdominal pain and found to have a palpable tumor. Computed tomography (CT) and colonoscopy revealed a combination of liver and colon lesions and colon cancer with a large liver metastasis was suspected. After neoadjuvant chemotherapy had proved ineffective for her presumed liver metastasis, the patient was referred to our hospital where we performed a simultaneous right hemicolectomy and extended left hepatic lobectomy. The pathological diagnoses were a colonic adenocarcinoma and retroperitoneal schwannoma immediately adjacent to the liver. Conclusions: Although liver metastasis should be the first provisional diagnosis in patients with advanced colon cancer, retroperitoneal schwannoma should also be suspected in the differential diagnosis of possible liver lesions..
102. Hiroshi Kobayashi, Yuka Kobayashi, Sho Yuasa, Masayuki Okabe, Yuichi Yamada, Yoshinao Oda, Maria Debiec-Rychter, Brian P. Rubin, Toshimitsu Suzuki, A Case of Undifferentiated Sarcoma in the Superior Vena Cava and Bilateral Cervical Veins, The American journal of case reports, 10.12659/AJCR.911659, 19, 1507-1514, 2018.12, BACKGROUND Intimal sarcoma (IS) is a malignant mesenchymal tumor with predominantly intraluminal growth in large vessels and the heart. Due to the rarity of cases it often poses diagnostic problems in clinical and pathological settings. Although the classification of IS is still controversial, undifferentiated type of IS has recently been found to show immunohistochemical positivity with MDM2, CDK4, or PDGFRA and amplification of MDM2/CDK4 and PDGFRA. CASE REPORT The patient was a 76 years-old Japanese man who presented with superior vena cava (SVC) syndrome. CT identified a tumor or thrombi in the SVC, bilateral brachiocephalic, and jugular veins. The histology of the biopsy specimen revealed an undifferentiated tumor without immunohistochemical positivity for all antibodies available except vimentin and smooth muscle actin. He was treated conservatively and died of respiratory failure 2 months after presentation. At autopsy, the large veins were filled by a sausage-like tumor and the cut sections revealed hemorrhagic and necrotic tumor. The tumor cells were negative with MDM2, CDK4, and PDGFRA by immunohistochemistry. Amplification of MDM2 and PDGFRA was not identified by fluorescence in-situ hybridization. CONCLUSIONS We concluded that the case was an undifferentiated sarcoma (IS without any specific phenotype) arising in the SVC, bilateral brachiocephalic, and jugular veins. We propose a way of subtyping sarcomas with predominantly intraluminal growth in large vessels and the heart based on immunohistochemistry and amplification of MDM2 and PDGFRA. However, proper subtyping of these sarcomas requires further study..
103. Daisuke Taniguchi, Hiroshi Saeki, Yuichiro Nakashima, Kensuke Kudou, Ryota Nakanishi, Nobuhide Kubo, Kouji Andou, Eiji Oki, Yoshinao Oda, Yoshihiko Maehara, CD44v9 is associated with epithelial-mesenchymal transition and poor outcomes in esophageal squamous cell carcinoma, Cancer Medicine, 10.1002/cam4.1874, 7, 12, 6258-6268, 2018.12, CD44 serves as a marker of cancer stem cells. Alternative splicing generates the CD44v9 isoform. Cancer stem cells are associated with the epithelial-mesenchymal transition in cancers, although little is known about their role in esophageal squamous cell carcinoma. Here, we aimed to clarify the relationship between CD44v9 expression, the epithelial-mesenchymal transition, and clinicopathological features of patients with esophageal squamous cell carcinoma. CD44v9 levels were higher at the tumor invasive front compared with the center of the tumor and higher in metastatic lymph nodes compared with primary tumors. High levels of CD44v9 at the tumor invasive front were significantly associated with deeper tumor invasion and shorter overall survival and recurrence-free survival. The expression of CD44v9 was increased by treatment with transforming growth factor-β, which induced esophageal squamous cell carcinoma cells to undergo the epithelial-mesenchymal transition. Moreover, inhibition of CD44v9 expression decreased the migration and invasiveness of esophageal squamous cell carcinoma cells. These results indicate that the expression of CD44v9 at the tumor invasive front induced by stemness was strongly associated with the epithelial-mesenchymal transition and poor prognosis of patients with esophageal squamous cell carcinoma. CD44v9 may therefore serve as a novel prognostic biomarker and a potential therapeutic target for esophageal squamous cell carcinoma..
104. Shinkichi Takamori, Kazuki Takada, Tetsuzo Tagawa, Gouji Toyokawa, Fumihiko Hirai, Nami Yamashita, Tatsuro Okamoto, Eiji Oki, Tomoharu Yoshizumi, Yoshinao Oda, Yoshihiko Maehara, Differences in PD-L1 expression on tumor and immune cells between lung metastases and corresponding primary tumors, Surgical Oncology, 10.1016/j.suronc.2018.08.001, 27, 4, 637-641, 2018.12, Background: It has been reported that the tumor microenvironment, including tumor-associated immune cells (ICs) and programmed cell death-ligand 1 (PD-L1) expression, differs between primary and metastatic tumors. This study aimed to elucidate the differences in PD-L1 expression on tumor cells (TCs) and ICs between lung metastases and corresponding primary tumors. Methods: We analyzed paired lesions from 44 patients diagnosed with lung metastases between 2005 and 2017 at Kyushu University. The percentages of PD-L1-positive TCs and ICs in lung metastases and the primary tumor were classified into five categories (0: <1%; 1: 1%–4%; 2: 5%–9%; 3: 10%–49%; and 4: ≥50%). Lesions in which ≥1% of the TCs and ICs were PD-L1-positive were considered positive. Results: The primary cancers included rectal (n = 19), colon (n = 10), liver (n = 10), bile duct (n = 2), stomach (n = 1), gall bladder (n = 1) and breast (n = 1). Discrepancies in PD-L1 expression on TCs and ICs between lung metastases and primary lesions were observed in 5 (11.4%, κ = 0.23) and 9 (20.5%, κ = 0.11) of the 44 cases, respectively. PD-L1 expression on ICs was higher in lung metastases than paired primary tumors (p = 0.026), although the percentage of PD-L1-positive TCs was not significantly different between lung metastases and primary tumors (p = 0.767). Conclusions: There were significant differences in PD-L1 expression on TCs and ICs between lung metastases and primary tumors. Clinicians should be aware of these differences in the tumor microenvironment when treating patients with immunotherapy..
105. Toshiya Abe, Kohei Nakata, Shin Kibe, Yasuhisa Mori, Yoshihiro Miyasaka, Kenoki Ouchida, Ohtsuka Takao, Yoshinao Oda, Masafumi Nakamura, Prognostic Value of Preoperative Nutritional and Immunological Factors in Patients with Pancreatic Ductal Adenocarcinoma, Annals of Surgical Oncology, 10.1245/s10434-018-6761-6, 25, 13, 3996-4003, 2018.12, Background: Preoperative nutritional and immunological patient factors have been found to be associated with prognostic outcomes of malignant tumors; however, the clinical significance of these factors in pancreatic ductal adenocarcinoma (PDAC) remains controversial. Objective: The aim of this study was to evaluate the prognostic value of nutritional and immunological factors in predicting survival of patients with PDAC. Methods: Retrospective studies of 329 patients who underwent surgical resection for PDAC and 95 patients who underwent palliative surgery were separately conducted to investigate the prognostic impact of tumor-related factors and patient-related factors, including Glasgow Prognostic Score (GPS), modified GPS, Prognostic Nutritional Index (PNI), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, and lymphocyte/monocyte ratio. Results: In multivariate analysis for patients with surgical resection for PDAC, PNI was an independent factor for overall survival (OS) and disease-free survival. The median OS of patients with PNI ≤ 45 was significantly shorter than that of patients with PNI > 45 (17.5 and 36.2 months, respectively; p < 0.001). In multivariate analysis for patients undergoing palliative surgery for PDAC, only NLR was an independent prognosis factor. The median OS of patients with NLR > 5 was significantly shorter than that of patients with NLR ≤ 5 (2.7 and 8.9 months, respectively; p < 0.001). Conclusions: PNI in patients with surgical resection and NLR in patients with palliative surgery for PDAC may be useful prognostic factors..
106. Hideaki Yahata, Hiroaki Kobayashi, Kenzo Sonoda, Keisuke Kodama, hiroshi yagi, Masafumi Yasunaga, Tatsuhiro Ogami, Ichiro Onoyama, Kaneki Eisuke, Okugawa Kaoru, Shingo Baba, Takuro Isoda, Yoshihiro Ohishi, Yoshinao Oda, Kiyoko Kato, Prognostic outcome and complications of sentinel lymph node navigation surgery for early-stage cervical cancer, International Journal of Clinical Oncology, 10.1007/s10147-018-1327-y, 23, 6, 1167-1172, 2018.12, Background: To evaluate the prognostic outcome and surgical complications in patients with early-stage cervical cancer who underwent sentinel node navigation surgery (SNNS) for hysterectomy or trachelectomy. Methods: A total of 139 patients who underwent SNNS using 99mTc phytate between 2009 and 2015 were evaluated. No further lymph node dissection was performed when intraoperative analysis of the sentinel lymph nodes (SLNs) was negative for metastasis. We compared the surgical complications between the SNNS group and 67 matched patients who underwent pelvic lymph node dissection (PLND) after SLN mapping between 2003 and 2008. We also examined the clinical outcomes in the SNNS group. Results: The mean number of detected SLNs was 2.5 per patient. Fourteen of the 139 patients in the SNNS group underwent PLND based on the intraoperative SLN results. The amount of blood loss, the operative time, and the number of perioperative complications were significantly less in the SNNS group than in the matched PLND group. There was no recurrence during a follow-up period ranging from 2 to 88 months (median 40 months) in the SNNS group. Conclusions: Using SNNS for early-stage cervical cancer is safe and effective and does not increase the recurrence rate. A future multicenter trial is warranted..
107. Kiyoshi Saeki, Yoshihiro Ohishi, Ryota Matsuda, Naoki Mochidome, Yoshihiro Miyasaka, Hidetaka Yamamoto, Yutaka Koga, Yoshihiko Maehara, Masafumi Nakamura, Yoshinao Oda, "pancreatic Mucoepidermoid Carcinoma" Is not a Pancreatic Counterpart of CRTC1/3-MAML2 Fusion Gene-related Mucoepidermoid Carcinoma of the Salivary Gland, and May More Appropriately be Termed Pancreatic Adenosquamous Carcinoma with Mucoepidermoid Carcinoma-like Features, American Journal of Surgical Pathology, 10.1097/PAS.0000000000001135, 42, 11, 1419-1428, 2018.11, "Mucoepidermoid carcinoma (MEC)" has been accepted as a synonym for pancreatic adenosquamous carcinoma (ASC). Pancreatic ASC can show salivary gland-type MEC-like morphology. CRTC1/3-MAML2 fusion gene is a characteristic molecular feature of MEC of the salivary gland. We conducted this study to clarify whether the pancreatic ASC with salivary gland-type MEC-like morphology (Pan-MEC) is a pancreatic counterpart of salivary gland-type MEC (Sal-MEC). We retrospectively analyzed 37 pancreatic ASCs including 16 Pan-MECs and 21 tumors without MEC-like features (ASC-NOS [not otherwise specified]), and we investigated (1) clinicopathologic features, (2) the presence of CRTC1/3-MAML2 fusion gene by reverse transcription polymerase chain reaction, (3) the presence of rearrangement of MAML2 gene by fluorescence in situ hybridization, and (4) mucin core proteins by immunohistochemistry. We also compared 16 Pan-MECs with 20 Sal-MECs by immunohistochemistry for mucin core protein. There were no significant differences of any clinicopathologic characteristics and survival analysis between the Pan-MECs and ASCs-NOS. Of note, the pancreatic ASCs (including Pan-MEC and ASC-NOS) were significantly more aggressive than conventional pancreatic ductal adenocarcinoma. In addition, all Pan-MECs were histologically high-grade. CRTC1/3-MAML2 fusion gene and MAML2 gene rearrangement were not detected in any ASCs including Pan-MECs. There were significant differences of MUC5AC and MUC6 between the Pan-MECs and Sal-MECs, but no significant differences of mucin core protein between the Pan-MECs and pancreatic ASCs-NOS. Pan-MEC is histologically and biologically high-grade and unrelated to CRTC1/3-MAML2 fusion gene, unlike Sal-MEC which is related to CRTC1/3-MAML2 fusion gene. Pan-MEC is not a pancreatic counterpart of CRTC1/3-MAML2 fusion gene-related Sal-MEC..
108. Eisuke Kawakubo, Takuya Matsumoto, Keiji Yoshiya, Sho Yamashita, Tomoko Jogo, Hiroshi Saeki, Eiji Oki, Tadashi Furuyama, Yoshinao Oda, Yoshihiko Maehara, BUBR1 insufficiency is correlated with eNOS reduction experimentally in vitro and in vivo, and in gastric cancer tissue, Anticancer research, 10.21873/anticanres.12960, 38, 11, 6099-6106, 2018.11, Background/Aim: Budding uninhibited by benzimidazole-related 1 (BUBR1) and endothelial nitric oxide synthase (eNOS) are related to aging and angiogenesis. This study examined the effect of low BUBR1 expression on eNOS expression in vivo, in vitro, and human gastric cancer tissues. Materials and Methods: Human umbilical vein endothelial cells (HUVECs) were passaged to investigate the effect of aging on BUBR1 and eNOS expression; expression of eNOS and phospho-eNOS protein was assessed in BUBR1 siRNAtransfected HUVECs. Additionally, guanosine 3′,5′ cyclic monophosphate (cGMP) and eNOS protein levels were measured in BUBR1-insufficient mice (Bubr1L/-). BUBR1 and eNOS expression levels were also evaluated in human gastric cancer tissues. Results: BUBR1 and eNOS, but not p-eNOS, levels were reduced significantly in aged and BUBR1 siRNAtransfected HUVECs. Additionally, cGMP production and the eNOS protein level were reduced in Bubr1L/- mice. Human gastric cancer tissues with low BUBR1 expression showed no eNOS expression. Conclusion: A decrease in BUBR1 reduced eNOS bioavailability through a pathway other than eNOS phosphorylation..
109. Kazuki Takada, Gouji Toyokawa, Koichi Azuma, Shinkichi Takamori, Tomoko Jogo, Fumihiko Hirai, Tetsuzo Tagawa, Akihiko Kawahara, Jun Akiba, Isamu Okamoto, Yoichi Nakanishi, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara, Radiological features of programmed cell death-ligand 2-positive lung adenocarcinoma
A single-institution retrospective study, In Vivo, 10.21873/invivo.11412, 32, 6, 1541-1550, 2018.11, Aim: Programmed cell death-ligand 1 and 2 (PD-L1 and PD-L2) are ligands of the programmed cell death- 1 (PD1) receptor. PD1/PD-L1 inhibitors have shown clinical efficacy in non-small cell lung cancer (NSCLC). However, relatively little is known about the expression of PD-L2, or its association with the clinicopathological features of NSCLC. Here, the radiological features of PD-L2-positive lung adenocarcinoma were evaluated. Materials and Methods: PDL1 and PD-L2 expression were evaluated by immunohistochemical staining of surgically-resected specimens from 393 patients with primary lung adenocarcinoma who underwent preoperative thin-section computed tomography (CT), 222 of whom also underwent 18F-fluorodeoxyglucose positron-emission tomography/CT (18F-FDG-PET/CT). Results: Among the 393 specimens, 132 (33.6%) and 266 (67.7%) were positive for PD-L1 and PD-L2 expression, respectively. Multivariate analysis showed that the absence of surrounding ground glass opacity and the presence of air bronchogram were significantly associated with PD-L2 expression; however, there was no significant association between PD-L2 expression and the consolidation/tumor ratio. In 222 18F-FDG-PET/CT, the maximum standardized uptake value was significantly higher in patients with PD-L2-positive compared to those with PD-L2-negative tumors. Conclusion: PD-L2-positive lung adenocarcinomas are less radiologically malignant and invasive than their PD-L1-positive counterparts..
110. Kentaro Nakashima, Yuhki Koga, Yasunari Sakai, Hidetoshi Takada, Katsumi Harimaya, Ohga Saiji, Tomoaki Taguchi, Yoshinao Oda, Hiroshi Honda, Shoichi Ohga, Radiotherapy for Langerhans cell histiocytosis with paraplegia
A rare oncologic emergency case report in infancy and literature review, Brain and Development, 10.1016/j.braindev.2018.05.016, 40, 10, 952-955, 2018.11, Background: Langerhans cell histiocytosis (LCH) is a clonal disease with focal or disseminated lesions that may compress the surrounding tissues, including the spinal cord. Because few reports have described the spinal symptoms as the first manifestation of pediatric LCH, the long-term neurological outcomes remain unclear. Case report and literature review: We report a 21-month-old boy who presented with sudden-onset paraplegia. Imaging analyses revealed that osteolytic lesions and epidural tumors compressing the spinal cord at the T7-9 vertebrae. Twelve days after he developed leg weakness, emergency radiotherapy was started after a tumor biopsy. During the course of radiotherapy, paralysis steadily ameliorated. After we excluded infections and determined the pathological diagnosis of LCH, multi-drug chemotherapy was started. Apparent improvement in his complete paraplegia was observed after a total 15 Gy of radiotherapy and subsequent chemotherapy, leaving no neurological sequelae at 4 years of age. Through a literature search of studies published from 1980 to 2017, we found that children with LCH showed a generally favorable recovery from neurological dysfunction after the acute phase of spinal symptoms. Conclusion: This report underscores the utility of emergency radiotherapy for the neurological recovery of spinal LCH in infants. Our long-term observation further denotes the value of this treatment in terms of the intact survival with preserved motor functions and physical growth..
111. Ryota Sozaki, Naonori Kawakubo, Kina Miyoshi, Satoshi Obata, Yoshiaki Kinoshita, Junkichi Takemoto, Kenichi Kouhashi, Yoshinao Oda, Tomoaki Taguchi, The utility of muscle-sparing axillar skin crease incision with thoracoscopic surgery in children, Journal of Laparoendoscopic and Advanced Surgical Techniques, 10.1089/lap.2018.0169, 28, 11, 1378-1382, 2018.11, Background: Thoracoscopic surgery for pediatric benign tumors is a common procedure. However, a large incision is needed to remove large tumors from the thoracic cavity. And, for intrapulmonary sequestration in lower lobe, it sometimes needs a large incision to ligate the aberrant vessels. A muscle-sparing axillar skin crease incision (MSASCI) has been introduced for thoracic open surgery, resulting in excellent aesthetic outcomes compared with a standard incision. We herein report the utility of this MSASCI technique in thoracoscopic surgery to remove large tumors from the thoracic cavity and to ligate the aberrant vessels in intrapulmonary sequestration in lower lobe. Materials and Methods: From 2014 April to 2016 March, we performed the MSASCI technique in thoracoscopic surgeries for 5 children. Result: Five cases were diagnosed as mediastinal masses (mature teratoma for 1 case, ganglioneuroblastoma for 2 cases, and extrapulmonary sequestration and intrapulmonary sequestration for 1 case each). The age at surgery was 32.0 ± 25.0 months (range 5-58 months). The size of the mediastinal mass was 9 × 5 × 5 cm, 4 × 3 × 3 cm, 5 × 5 × 2.5 cm, and 3 × 2.5 × 2 cm. For 4 other cases, except for the intrapulmonary sequestration case, the mass was resected under thoracoscopic surgery using only three or four 5-mm trocars and the mass was removed from the thoracic cavity using the MSASCI technique. For the intrapulmonary sequestration case, the aberrant vessels were resected under thoracoscopic surgery using only two 5-mm and one 12-mm trocars and the left lower lobectomy was performed using the MSASCI technique. All lesions were resected completely. No cases had surgical complications, none showed recurrence, and all cases demonstrated good cosmetic outcomes. Conclusions: Performing thoracoscopic surgery using a MSASCI technique is associated with good cosmetic outcome..
112. Tatsuro Abe, Kenichi Kohashi,Junkichi Takemoto, Fumio Kinoshita, Masatoshi Eto,and Yoshinao Oda, Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor., J Cancer, 10.7150/jca.25279, 2018.11.
113. Hitomi Mori, Makoto Kubo, Masaya Kai, Vittoria Vanessa Velasquez, Kanako Kurata, Mai Yamada, Masayuki Okido, Syoji Kuroki, Yoshinao Oda, Masafumi Nakamura, BRCAness Combined With a Family History of Cancer Is Associated With a Poor Prognosis for Breast Cancer Patients With a High Risk of BRCA Mutations, Clinical Breast Cancer, 10.1016/j.clbc.2018.05.008, 18, 5, e1217-e1227, 2018.10, We assessed BRCAness as a characteristic of BRCA-mutated breast cancer. We investigated 124 breast cancer patients with a high risk of BRCA mutations, who had early-onset or triple-negative breast cancer. No correlation was found between BRCAness and family history. However, those with a BRCAness tumor and a positive family history had a significantly worse prognosis, which could be of use in predicting the prognosis. Background: The inexpensive prediction of the characteristics of BRCA-mutated breast cancer as “BRCAness” using the somatic cells of patients with breast cancer could be useful for developing a therapeutic strategy. Our objective was to correlate BRCAness with the clinicopathologic features, including a family history (FH) of cancer, in breast cancer patients with a high risk of BRCA mutations. Patients and Methods: The present study included 124 patients, including 55 with early-onset and 77 with triple-negative breast cancer, who had undergone resection at Kyushu University Hospital from 2005 to 2014. Early-onset breast cancer is defined as an onset in patients aged ≤ 40 years. BRCAness was performed using multiple ligation-dependent probe amplification. The patients’ FH of cancer was surveyed from first- to third-degree relatives. Results: Of the 124 patients, the multiple ligation-dependent probe amplification assay results indicated that 59 tumors (47.6%) had BRCAness and 27 patients (21.8%) had a positive FH for cancer. The patients with BRCAness experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) compared with those without. Patients with FH had shorter RFS and OS compared to those without BRCAness. The patients were divided into those with and without BRCAness and those with and without a positive FH. The BRCAness with FH subgroup experienced significantly shorter RFS and OS. Multivariate analysis revealed that BRCAness and a positive FH were independent negative prognostic factors. Conclusion: Our findings suggest that BRCAness tumors with a positive FH of cancer were associated with a poor prognosis in the BRCA-mutation high-risk group. We propose that BRCAness and a positive FH will serve to predict patients’ prognosis..
114. Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Takeshi Kamitani, Yuzo Yamasaki, Mototsugu Shimokawa, Yoshinao Oda, Yoshihiko Maehara, Computed tomography features of resected lung adenocarcinomas with spread through air spaces, Journal of Thoracic and Cardiovascular Surgery, 10.1016/j.jtcvs.2018.04.126, 156, 4, 1670-1676.e4, 2018.10, Background: Spread through air spaces (STAS) is a recently recognized invasive pattern of lung cancer defined as “micropapillary clusters, solid nests, or single cells beyond the edge of the tumor into air spaces.” Since STAS has been shown to be a significant prognosticator for the postoperative survival, predicting STAS preoperatively by computed tomography (CT) might help determine the optimum surgical procedures. Methods: Information on STAS and preoperative CT was available in 327 patients with resected lung adenocarcinomas. STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. The association of STAS with CT characteristics, such as vascular convergence, ground-glass opacity (GGO), air bronchogram, notch, pleural indentation, spiculation, and cavitation, was analyzed. Results: Among the 327 patients with resected adenocarcinoma, 191 (58.4%) were positive for STAS. A univariable analysis demonstrated that STAS-positive adenocarcinomas were significantly associated with a larger radiologic tumor diameter (P =.02), the presence of vascular convergence (P <.01), notch (P <.01), pleural indentation (P =.03), spiculation (P <.01), and the absence of GGO (P <.01) compared with STAS-negative ones. In a multivariable analysis, the presence of notch (P =.01) and the absence of GGO (P <.01) were shown to be significantly associated with the STAS phenomenon. The odds ratio for STAS of notch-positive and GGO-negative adenocarcinomas against notch-negative and GGO-positive ones was 5.01 (P <.01). Conclusions: The presence of notch and the absence of GGO were independently associated with the STAS phenomenon. These results will prove helpful in identifying STAS-positive adenocarcinoma by CT before surgical resection..
115. Kenji Tsuchihashi, Shuji Arita, Minako Fujiwara, Kazuhide Iwasaki, Atsushi Hirano, Tomoyasu Yoshihiro, Kenta Nio, Yutaka Koga, Motohiro Esaki, hiroshi ariyama, Hitoshi Kusaba, Taiki Moriyama, Kenoki Ouchida, Eishi Nagai, Masafumi Nakamura, Yoshinao Oda, Koichi Akashi, Eishi Baba, Metastatic esophageal carcinosarcoma comprising neuroendocrine carcinoma, squamous cell carcinoma, and sarcoma A case report, Medicine (United States), 10.1097/MD.0000000000012796, 97, 41, 2018.10, Rationale: Esophageal carcinosarcoma generally comprises 2 histological components: squamous cell carcinoma (SqCC) and sarcoma. Esophageal carcinosarcoma comprising 3 components is extremely rare and no reports have described therapeutic effects for this disease with metastasis. Patient concerns: A 76-year-old man with dysphagia presented to a local clinic. Gastrointestinal endoscopy revealed a polypoid tumor in the middle esophagus and he was referred to our hospital. Diagnosis and Interventions: Thoracoscopic esophagectomy with super-extended (D3) nodal dissection and gastric tube reconstitution was performed, which resulted in carcinosarcoma comprising neuroendocrine carcinoma (NEC), SqCC, and sarcoma. Pathological stage was T1bN1M0 stage IIB according to the TNM Classification of Malignant Tumors-7th edition. The NEC component was observed in lymph node. At 47 days after surgery, lymph nodes, liver, and bone metastasis appeared, and tumor markers such as ProGRP and NSE were elevated. Combination chemotherapy with cisplatin and etoposide (EP) adapted to NEC was performed. Outcomes: The patient showed complete response within 4 cycles of chemotherapy. However, the disease recurred 5.5 months after the final course of EP chemotherapy. Lessons: A therapeutic strategy based on assessment of which component caused metastasis might be important for metastatic carcinosarcoma comprising 3 components, although more accumulation of data about the efficacy of chemotherapy is necessary. Moreover, elucidation of the mechanisms underlying generation of carcinosarcoma is expected in the future..
116. Shinkichi Takamori, Kazuki Takada, Gouji Toyokawa, Koichi Azuma, Mototsugu Shimokawa, Tomoko Jogo, Yuichi Yamada, Fumihiko Hirai, Tetsuzo Tagawa, Akihiko Kawahara, Jun Akiba, Isamu Okamoto, Yoichi Nakanishi, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara, PD-L2 expression as a potential predictive biomarker for the response to anti-PD-1 drugs in patients with non-small cell lung cancer, Anticancer research, 10.21873/anticanres.12933, 38, 10, 5897-5901, 2018.10, Background/Aim: To investigate the role of programmed cell death-ligand 2 (PD-L2) expression as a predictive biomarker for response to anti-programmed cell death-1 (PD-1) drugs in patients with non-small cell lung cancer (NSCLC). Patients and Methods: Ten patients who had undergone curative lung resection and received the anti-PD-1 drugs for the recurrence were enrolled. The cut-off value for PD-L2 (antibody clone 176611) expression on tumor cells was set at 50%. Tumor response was evaluated according to immune-related response criteria. Results: Seven patients (70.0%) were positive for PD-L2. The response rates were 28.6% (2/7) and 33.3% (1/3) in patients with PD-L2-positive and PD-L2-negative NSCLC, respectively. Disease control was obtained in 2 patients despite the programmed cell deathligand 1 (PD-L1)-negativity (antibody clone 22C3: 0%, antibody clone SP142: 0%), and these tumors expressed PDL2 (=1%). Conclusion: PD-L2 expression may be a target of immunotherapy in patients with PD-L1-negative NSCLC..
117. Shinkichi Takamori, Kazuki Takada, Koichi Azuma, Yumiko Jogo, Fumihiko Kinoshita, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Gouji Toyokawa, Fumihiko Hirai, Tetsuzo Tagawa, Isamu Okamoto, Yoichi Nakanishi, Akihiko Kawahara, Jun Akiba, Yoshinao Oda, Yoshihiko Maehara, Prognostic impact of PD-L2 expression and association with PD-L1 in patients with small-cell lung cancer, Anticancer research, 10.21873/anticanres.12934, 38, 10, 5903-5907, 2018.10, Background/Aim: Although some previous studies suggested that programmed cell death-ligand 1 (PD-L1) expression was significantly associated with a favorable postoperative prognosis in patients with smallcell lung cancer (SCLC), the prognostic significance of PDL2 expression remains unknown. The aim of the current study was to investigate the prognostic significance of PDL2 expression in patients with SCLC. Patients and Methods: Thirty-eight patients who underwent resection of SCLC were analyzed. A monoclonal anti-human PD-L1 antibody (clone SP142) and a monoclonal anti-human PDL2 antibody (clone 176611) were used as the primary antibodies. Cut-off value for PD-L1 and PD-L2 expression was set to 1%. Results: Among 38 patients, 15 (39.5%) were positive for PD-L2 expression. No significant associations between PD-L2-positivity and clinicopathological factors, including PD-L1 positivity or prognosis were identified. No significant differences in disease-free survival and overall survival were observed between PD-L2-positive patients and PD-L2-negative patients (p=0.367 and p=0.726, respectively). Conclusion: PD-L2 expression is not related to clinicopathological factors or postoperative prognosis in patients with SCLC, though this should be further investigated in studies involving larger populations..
118. Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Yoshinao Oda, Significance of spread through air spaces in early-stage lung adenocarcinomas undergoing limited resection, Thoracic Cancer, 10.1111/1759-7714.12828, 9, 10, 1255-1261, 2018.10, Background: In early-stage lung adenocarcinomas, spread through air spaces (STAS) are reported to be a prognostic factor in patients who have undergone sublobar resection, but not lobectomy. In contrast, reports have also shown that STAS is significantly associated with poor survival outcomes after lobectomy, but not after limited resection. Thus, the prognostic impact of STAS differs according to published reports. Methods: A total of 82 patients with early-stage adenocarcinomas who underwent limited resection and whose STAS status could be examined were enrolled in this retrospective study. We evaluated the association between STAS and clinicopathological characteristics and postoperative survival. Results: Among 82 patients, 31 (37.8%) were positive for STAS, while 51 (62.2%) were negative. STAS was significantly associated with advanced tumor stage (P < 0.01), lower histological differentiation (P = 0.01), and the presence of pleural invasion (P = 0.01). Patients with STAS had significantly shorter recurrence-free survival (RFS) and overall survival (OS) than those without STAS (P < 0.01 and P = 0.02, respectively). According to multivariate analysis, positivity for STAS was an independent prognostic parameter for RFS (P < 0.01), but not OS (P = 0.45). Three patients who developed surgical margin recurrence and one patient who developed distant recurrence were all positive for STAS. Conclusions: STAS was predictive of poor postoperative survival in patients with early-stage adenocarcinomas treated with limited resection and was associated with surgical margin recurrence..
119. Yuka Yoshida, Sumihito Nobusawa, Satoshi Nakata, Mitsutoshi Nakada, Yoshiki Arakawa, Yohei Mineharu, Yasuo Sugita, Takako Yoshioka, Asuka Araki, Yuichiro Sato, Hideo Takeshima, Masahiko Okada, Akira Nishi, Tatsuya Yamazaki, Kenichi Kouhashi, Yoshinao Oda, Junko Hirato, Hideaki Yokoo, CNS high-grade neuroepithelial tumor with BCOR internal tandem duplication
a comparison with its counterparts in the kidney and soft tissue, Brain Pathology, 10.1111/bpa.12585, 28, 5, 710-720, 2018.09, Central nervous system high-grade neuroepithelial tumors with BCOR alteration (CNS HGNET-BCOR) are a recently reported rare entity, identified as a small fraction of tumors previously institutionally diagnosed as so-called CNS primitive neuroectodermal tumors. Their genetic characteristic is a somatic internal tandem duplication in the 3′ end of BCOR (BCOR ITD), which has also been found in clear cell sarcomas of the kidney (CCSK) and soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and these BCOR ITD-positive tumors have been reported to share similar pathological features. In this study, we performed a clinicopathological and molecular analysis of six cases of CNS HGNET-BCOR, and compared them with their counterparts in the kidney and soft tissue. Although these tumors had histologically similar structural patterns and characteristic monotonous nuclei with fine chromatin, CNS HGNET-BCOR exhibited glial cell morphology, ependymoma-like perivascular pseudorosettes and palisading necrosis, whereas these features were not evident in CCSK or URCS/PMMTI. Immunohistochemically, diffuse staining of Olig2 with a mixture of varying degrees of intensity, and only focal staining of GFAP, S-100 protein and synaptophysin were observed in CNS HGNET-BCOR, whereas these common neuroepithelial markers were negative in CCSK and URCS/PMMTI. Therefore, although CNS HGNET-BCOR, CCSK and URCS/PMMTI may constitute a group of BCOR ITD-positive tumors, only CNS HGNET-BCOR has histological features suggestive of glial differentiation. In conclusion, we think CNS HGNET-BCOR are a certain type of neuroepithelial tumor relatively close to glioma, not CCSK or URCS/PMMTI occurring in the CNS..
120. Yuka Kozuma, Kazuki Takada, Gouji Toyokawa, Kenichi Kouhashi, Mototsugu Shimokawa, Fumihiko Hirai, Tetsuzo Tagawa, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara, Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma, European Journal of Cancer, 10.1016/j.ejca.2018.06.020, 101, 20-29, 2018.09, Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression. Materials and methods: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis. Results: IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that ≥1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-γ and transforming growth factor-β. Conclusion: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma..
121. Yurie Mikami, Shinsuke Fujii, Kenichi Kouhashi, Yuichi Yamada, Masafumi Moriyama, Shintarou Kawano, Seiji Nakamura, Yoshinao Oda, Tamotsu Kiyoshima, Low grade myofibroblastic sarcoma arising in the tip of the tongue with intravascular invasion
A case report, Oncology Letters, 10.3892/ol.2018.9115, 16, 3, 3889-3894, 2018.09, Low grade myofibroblastic sarcoma (LGMS) is a rare intermediate tumor, which rarely metastasizes and has myofibroblastic differentiation in various sites. It is particularly associated with the tongue in the head and neck region. The lack of any pathological features means it is difficult to make a conclusive diagnosis of LGMS. The immunohistochemical features and genomic rearrangements, including SS18 SSXs and MYH9 USP6s and the genetic mutations of cancer associated genes, including APC, CTNNB1, EGFR, KRAS, PIK3CA and p53 were examined in a case of LGMS arising in the tip of the tongue. Immunohistochemically, the tumor cells were positive for alpha smooth muscle actin and vimentin, as in previous reports. They demonstrated neither genomic rearrangements nor point mutations of cancer associated genes. Although several tumor cells demonstrated intravascular invasion, the MIB l labeling index of the cells was the same as the original lesion. To the best of our knowledge, this is the first case report of LGMS arising in the tip of the tongue with intravascular invasion..
122. Kazuki Takada, Gouji Toyokawa, Tetsuzo Tagawa, Mototsugu Shimokawa, Kenichi Kouhashi, Akira Haro, Atsushi Osoegawa, Yoshinao Oda, Yoshihiko Maehara, Radiological features of IDO1+/PDL1+ lung adenocarcinoma
A retrospective single-institution study, Anticancer research, 10.21873/anticanres.12856, 38, 9, 5295-5303, 2018.09, Aim: A combination of immune-checkpoint inhibitors that target the programmed cell death 1 (PD1)/programmed cell-death ligand 1 (PDL1) pathway and indoleamine 2,3-dioxygenase 1 (IDO1) is a promising treatment for non-small-cell lung cancer. Herein, we investigated clinical features of IDO1+/PDL1+ primary lung adenocarcinoma. Materials and Methods: IDO1 and PDL1 expression in 388 resected primary lung adenocarcinoma samples was evaluated using immunohistochemistry, and the radiological features of patients with IDO1+/PDL1+ lung adenocarcinoma were analyzed. Results: Of 388 specimens, 229 (59.0%) were IDO1+, 131 (33.8%) were PDL1+, and 109 (28.1%) were IDO1+/PDL1+. In multivariate analysis, vascular convergence and the absence of surrounding ground glass opacity were significantly associated with IDO1+/PDL1+ tumors. Fisher’s exact test showed high consolidation/tumor ratio was also significantly associated with IDO1+/PDL1+ tumors. Moreover, maximum standardized uptake in18F-fluorodeoxyglucose positron-emission tomography/computed tomography was significantly higher in patients with IDO1+/PDL1+ tumors than in those with IDO1 or PDL1 tumors. Conclusion: IDO1/PDL1 co-expression was significantly related to radiological invasiveness and malignancy in lung adenocarcinoma. This study may help select patients likely to benefit from combination therapy using immune-checkpoint inhibitors..
123. Kimitaka Nakamura, Masanobu Ohishi, Tomoya Matsunobu, Yasuharu Nakashima, Akio Sakamoto, Akira Maekawa, Yoshinao Oda, Yukihide Iwamoto, Tumor-induced osteomalacia caused by a massive phosphaturic mesenchymal tumor of the acetabulum
A case report, Modern Rheumatology, 10.3109/14397595.2016.1173322, 28, 5, 906-910, 2018.09, We report a case of tumor-induced osteomalacia (TIO) caused by a massive phosphaturic mesenchymal tumor (PMT) of the acetabulum. A 68-year-old woman presented with progressive bone pain of the rib cage, and polyarthralgia and back pain for 3 years. She was diagnosed with hypophosphatemic osteomalacia because laboratory testing was remarkable for low serum phosphorus and a low level of 1,25(OH)2 vitamin D. Three years later, her hip radiograph revealed an osteolytic lesion of the acetabulum. Magnetic resonance imaging of the acetabulum showed a massive lesion. Laboratory data showed hypophosphatemia and an elevated serum level of fibroblast growth factor 23 (FGF-23). Samples obtained with open biopsy showed a low-grade spindle cell neoplasm with FGF-23 positivity, identified by using immunohistochemical staining, confirming the diagnosis of a PMT mixed connective tissue variant. Curettage of the tumor was performed, and the defects were filled with bone allografts. The hip joint was reconstructed with total hip arthroplasty using a Muller support ring. To our knowledge, this report represents the first documented case of massive PMT of the acetabulum causing TIO..
124. Yuka Inoue, Nami Yamashita, Hiroyuki Kitao, Kimihiro Tanaka, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Eriko Tokunaga, Yoshihiko Maehara, Clinical Significance of the Wild Type p53-Induced Phosphatase 1 Expression in Invasive Breast Cancer, Clinical Breast Cancer, 10.1016/j.clbc.2017.11.008, 18, 4, e643-e650, 2018.08, The nuclear expression of wild type p53-induced phosphatase 1 (Wip1) protein was found to be positive in 21 patients (10.4%) out of 201 breast cancer patients in our study. The protein phosphatase magnesium dependent 1 delta DNA copy number was significantly correlated with Wip1 protein expression, which was positively correlated with p21 expression. Tumors with positive Wip1 expression and negative p21 expression showed the poorest prognosis of all tumors examined. Background: Wild type p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase magnesium dependent 1 delta (PPM1D), inhibits p53. PPM1D amplification has been reported in breast cancer. Breast cancer can sometimes develop without a tumor protein 53 (TP53) mutation. In these cases, the p53 pathway might be disrupted by alternative mechanisms, and Wip1 is reported to be a key molecule involved. Materials and Methods: Primary invasive ductal carcinoma specimens were obtained from 201 cases, for which archival tissue samples for immunohistochemistry were available. We evaluated Wip1 and p21 protein expression (201 cases), Wip1 mRNA expression (63 cases), PPM1D DNA copy number (71 cases) and TP53 status (36 cases) using available samples among the 201 cases, and analyzed their relationships with clinicopathological factors and prognosis. Results: The nuclear expression of Wip1 protein was positive in 21 cases (10.4%). The PPM1D DNA copy number was significantly correlated with Wip1 protein expression. All cases with PPM1D amplification by single-nucleotide polymorphism comparative genomic hybridization array showed positive nuclear Wip1 expression. Wip1 protein expression was positively correlated with p21 expression. The tumors with positive Wip1 and negative p21 expression showed the poorest prognosis among all tumor types. Conclusion: The protein expression of Wip1 might be regulated by PPM1D amplification, independent of TP53 status. Positive Wip1 and negative p21 expression was associated with the poorest prognosis and suggests the loss of p53 function..
125. Tetsuyuki Miyazaki, Shinichi Aishima, Minoru Fujino, Keigo Ozono, yuichiro kubo, yasuhiro ushijima, Takashi Osoegawa, Eikichi Ihara, Itou Tetsuhide, Ohtsuka Takao, Masafumi Nakamura, Yoshinao Oda, Neuroendocrine tumor of the pancreas with rhabdoid feature, Virchows Archiv, 10.1007/s00428-018-2398-x, 473, 2, 247-252, 2018.08, Imaging of a 53-year-old Japanese man revealed two tumors in the liver and a tumor in the head of the pancreas with a swelling lymph node. A needle biopsy for the liver tumors was performed, revealing a neuroendocrine tumor. Enucleation, lymphadenectomy, and partial hepatectomy were performed. The microscopic examination identified many tumor cells with intracytoplasmic inclusions arranged in a nested, cord, or tubular fashion. The intracytoplasmic inclusions displayed densely eosinophilic globules and displaced the nuclei toward the periphery, which constitutes “rhabdoid” features. The tumor cells were positive for synaptophysin and weakly positive for NCAM, but negative for chromogranin A. Epithelial markers (AE1/AE3 and CAM5.2) accentuated intracytoplasmic globules. Pancreatic neuroendocrine tumors with rhabdoid features are very rare. Generally, rhabdoid features are aggressive and dedifferentiated characteristics of various types of tumor. Pancreatic neuroendocrine tumors containing rhabdoid cells tend to display extrapancreatic spread at the time of presentation, although some of these tumors with rhabdoid features are not always associated with aggressive behavior..
126. Yoshiteru Kumagae, Minako Hirahashi, Katsumi Takizawa, Hidetaka Yamamoto, Masaki Gushima, Motohiro Esaki, Takayuki Matsumoto, Masafumi Nakamura, Takanari Kitazono, Yoshinao Oda, Overexpression of mth1 and ogg1 proteins in ulcerative colitis-associated carcinogenesis, Oncology Letters, 10.3892/ol.2018.8812, 16, 2, 1765-1776, 2018.08, Oxidative stress, demonstrated by an accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), results in DNA damage, which is normally repaired by base excision repair enzymes including 8-OHdG DNA glycosylase (OGG1) and human MutY homolog (MUTYH), in addition to nucleotide pool sanitizing enzymes including MutT Homolog 1 (MTH1). Abnormalities of this repair system are present in various cancer types. The present study aimed to elucidate the clinicopathological significance of altered expression levels of inducible nitric oxide synthase (iNOS), 8-OHdG, OGG1, MTH1 and MUTYH in ulcerative colitis (UC) and UC-associated neoplasms. Immunohistochemical staining for these markers and p53 in 23 cases of UC-associated neoplasm (Group A, 14 carcinomas and nine dysplasias), 16 cases of UC without neoplasm (Group B) and 17 cases of normal colon specimens (Group C) was performed. Mutation analyses was conducted for KRAS proto-oncogene, GTPase (K-ras), tumor protein P53 (TP53) and isocitrate dehydrogenase (NADP (+)) 1, cytosolic (IDH1) genes. Immunohistochemically, the iNOS, 8-OHdG, OGG1 and MTH1 expression levels were increased in Groups A and B compared with Group C. The OGG1 and MTH1 expression levels in Group A were also increased compared with Group B. Group A and Group B exhibited increased cytoplasmic expression and decreased nuclear expression of MUTYH compared with Group C. Mutations of K-ras and TP53 were detected in 2/21 (9.5%) and 10/22 (45.5%) cases of Group A, respectively. IDH1 mutation was not detected in any cases. These findings suggest that, as a response to oxidative damage, OGG1 and MTH1 may be upregulated in UC through an inflammatory condition that progresses to cancer formation. Persisting oxidative damage stress may play a role in the pathogenesis of UC-associated tumors..
127. Hideto Teranishi, Yuhki Koga, Kentaro Nakashima, Eiji Morihana, Kanako Ishii, Yasunari Sakai, Tomoaki Taguchi, Yoshinao Oda, Noriko Miyake, Naomichi Matsumoto, Shoichi Ohga, Cancer management in kabuki syndrome
The first case of wilms tumor and a literature review, Journal of Pediatric Hematology/Oncology, 10.1097/MPH.0000000000001111, 40, 5, 391-394, 2018.07, A 3-year-old Japanese girl treated for hypoplastic left heart syndrome and Dandy-Walker syndrome was diagnosed with Kabuki syndrome (KS) with a mutation of KMT2D; c.13285C>T:p.Q4429∗. Concurrently, macrohematuria portended the diagnosis of Wilms tumor. Postoperative chemotherapy has achieved complete remission despite a prolonged and reduced regimen due to liver dysfunction and convulsions. Cancer predisposition has been suggested for KS due to oncogenic mutations in KMT2D or KDM6A. The first case of nephroblastoma exemplified the treatability of malignancies in KS patients, as shown in the 9 cases reviewed. Active screening and intervention are recommended for the cure of malignancy in KS children..
128. Kentaro Tanaka, Toyoshi Yanagihara, Yuki Ikematsu, Hiroyuki Inoue, keiichi ota, Eiji Kashiwagi, Kunihiro Suzuki, Naoki Hamada, ario takeuchi, Katsunori Tatsugami, Masatoshi Eto, Kayo Ijichi, Yoshinao Oda, Kohei Otsubo, Yasuto Yoneshima, Eiji Iwama, Yoichi Nakanishi, Isamu Okamoto, Detection of identical T cell clones in peritumoral pleural effusion and pneumonitis lesions in a cancer patient during immune-checkpoint blockade, Oncotarget, 10.18632/oncotarget.25743, 9, 55, 30587-30593, 2018.07, Although immune-related adverse events (irAEs) of treatment with immunecheckpoint inhibitors may be due to cellular immunity mediated by T lymphocytes, their pathogenesis has remained unknown. Here we collected bronchoalveolar lavage fluid (BALF) from a cancer patient with nivolumab-induced pneumonitis and isolated mononuclear cells for next-generation sequencing of the complementarity-determining region of the T cell receptor (TCR) β chain. Mononuclear cells in peritumoral pleural effusion isolated from the patient were similarly analyzed, and the results obtained for the two specimens were compared. A substantial number of TCRβ clones in BALF were also identified among lymphocytes in the peritumoral pleural effusion. Such a correlation was not apparent between TCRβ clones in BALF and those in peripheral blood. Moreover, many tumor-associated clones with a read frequency of =0.10% were also present in BALF. Our data suggest that irAEs might be induced by drugactivated lymphocytes originating from tumor tissue. Deep sequencing will thus be indispensable for investigations of the immune-based pathogenesis of, and the development of optimal treatments for, irAEs..
129. Shinkichi Takamori, Tetsuzo Tagawa, Gouji Toyokawa, Hiroki Ueo, Mototsugu Shimokawa, Fumihiko Kinoshita, Taichi Matsubara, Yuka Kozuma, Naoki Haratake, Takaki Akamine, Masakazu Katsura, Kazuki Takada, Fumihiko Hirai, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara, The significant influence of having children on the postoperative prognosis of patients with nonsmall cell lung cancer
A propensity score-matched analysis, Cancer Medicine, 10.1002/cam4.1539, 7, 7, 2860-2867, 2018.07, The aim of this study was to elucidate the relationship between family-associated factors and the postoperative prognosis in patients with nonsmall cell lung cancer (NSCLC). Additionally, we investigated whether having children was associated with the postoperative maintenance of the nutritional status. We selected 438 NSCLC patients who had undergone curative lung resection between 2004 and 2011 at Kyushu University (Fukuoka, Japan), whose family-associated factors were available. Nutritional indices, including the prognostic nutritional index (PNI), were used to estimate the change in the nutritional status for 1 year after surgery. A propensity score analysis was conducted after adjusting the following variables: sex, age, smoking history, performance status, pathological stage, and histological type. Three hundred patients (68.5%) had both children and partners. Forty-nine patients (11.2%) only had children, and 56 (12.8%) patients only had a partner. Thirty-three patients (7.5%) did not have a partner or children. The overall survival (OS) and disease-free survival (DFS) of the partner-present and partner-absent patients did not differ to a statistically significant extent (P =.862 and P =.712, respectively). However, childless patients showed significantly shorter OS and DFS in comparison with patients with children (P =.005 and P =.002, respectively). The postoperative exacerbation of PNI was significantly greater in childless patients than in patients with children (P =.003). These results remained after propensity score matching. Childless patients had a significantly poorer postoperative prognosis than those with children. Surgeons caring for childless NSCLC patients should be aware of the poorer postoperative outcomes in this population..
130. Nobuhiro Torata, Makoto Kubo, Daisuke Miura, Kenoki Ouchida, yusuke mizuuchi, Yoshinori Fujimura, Eisuke Hayakawa, Masaya Kai, Yoshinao Oda, Kazuhiro Mizumoto, Makoto Hashizume, Masafumi Nakamura, Visualizing energy charge in breast carcinoma tissues by MALDI mass-spectrometry imaging profiles of low-molecular-weight metabolites, Anticancer research, 10.21873/anticanres.12723, 38, 7, 4267-4272, 2018.07, Background/Aim: Metabolomics is widely used for biomarker discovery, but conventional mass-spectrometry extraction procedures lose the spatial localization of metabolites. In this study, we directly analyzed breast carcinoma tissues embedded in frozen tissue microarrays (fTMAs) using MALDI mass-spectrometry imaging (MALDI-MSI). Materials and Methods: A total of 119 breast tissues (84 carcinoma and 35 normal) were used. MSI data were extracted from each tissue. Results: Overall, 185 of 1,915 peaks which were commonly detected in 60% of target areas were subjected to further analysis. One hundred and fifty-two peaks of carcinoma showed significantly higher intensity than normal. Comparing metabolite profiles from carcinoma and normal tissues, energy charge (EC) and the sum of adenosine phosphate compound (AXP) indicated significantly higher intensities in cancerous tissues than normal. But comparisons of EC and AXP among lymph node metastasis, tumor size and tumor subtypes indicated no significant differences. Conclusion: Breast carcinoma tissues had higher EC and AXP values than normal. MALDI-MSI could be a tool for characterizing breast carcinoma..
131. Hirofumi Watanabe, Yoshiki Asayama, Akihiro Nishie, Kosei Ishigami, yasuhiro ushijima, Daisuke Okamoto, nobuhiro fujita, Tomoharu Yoshizumi, Yoshinao Oda, Hiroshi Honda, A case of pseudoglandular hepatocellular carcinoma
The usefulness of a multimodal approach, Radiology Case Reports, 10.1016/j.radcr.2018.03.022, 13, 3, 689-692, 2018.06, Hepatocellular carcinoma (HCC) mainly composed of the pseudoglandular pattern is very rare. We present a case of pseudoglandular HCC that was hyperechoic on ultrasound, with strongly high signal intensity on T2-weighted imaging and weak arterial contrast enhancement. Computed tomography hepatic arteriography showed corona enhancement. Radiologists should keep in mind this combination of multimodal radiological findings for pseudoglandular HCC..
132. Daisuke Shiraishi, Yukio Fujiwara, Hasita Horlad, Yoichi Saito, Toyohisa Iriki, Junko Tsuboki, Pan Cheng, Naomi Nakagata, Hiroshi Mizuta, Hirofumi Bekki, Yasuharu Nakashima, Yoshinao Oda, Motohiro Takeya, Yoshihiro Komohara, CD163 is required for protumoral activation of macrophages in human and murine sarcoma, Cancer Research, 10.1158/0008-5472.CAN-17-2011, 78, 12, 3255-3266, 2018.06, Recent findings have shown the significance of CD163-positive macrophages in tumor progression, yet there have been few studies on the function of CD163 in macrophages. Here, we uncover the role of CD163 in macrophage activation using CD163-deficient mice and human samples. We detected CD163 in 62 undifferentiated pleomorphic sarcoma samples, in which a high percentage of CD163-positive macrophages was associated with decreased overall survival and higher histologic grade. We observed macrophage-induced tumor cell proliferation in cocultures of human monocyte-derived macrophages and leiomyosarcoma (TYLMS-1) and myxofibrosarcoma (NMFH-1) cell lines, which was abrogated by silencing of CD163. Tumor development of sarcoma (MCA205 and LM8) cells in CD163-deficient mice was significantly abrogated in comparison with wild-type (WT) mice. Coculture with WT peritoneal macrophages significantly increased proliferation of MCA205 cells but decreased in the presence of CD163-deficient macrophages. Production of IL6 and CXCL2 in CD163-deficient macrophages was suppressed in comparison withWTmacrophages, and overexpression of CD163 in CD163-deficient macrophages induced production of IL6 and CXCL2. Silencing of IL6 but not CXCL2 abrogated macrophageinduced proliferation ofMCA205 cells. Taken together, our results show that CD163 is involved in protumoral activation of macrophages and subsequent development and progression of tumors in mice and humans. Significance: Macrophage CD163-mediated induction of IL6 promotes tumor development and progression in murine and human malignant tumors..
133. Gouji Toyokawa, Kazuki Takada, Tetsuzo Tagawa, Fumihiko Kinoshita, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Fumihiko Hirai, Yuichi Yamada, Ryuji Hamamoto, Yoshinao Oda, Yoshihiko Maehara, Prevalence of enhancer of zeste homolog 2 in patients with resected small cell lung cancer, Anticancer research, 10.21873/anticanres.12649, 38, 6, 3707-3711, 2018.06, Background/Aim: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated. Patients and Methods: Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals. Results: Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher’s exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients. Conclusion: EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals..
134. Shinkichi Takamori, Gouji Toyokawa, Mototsugu Shimokawa, Fumihiko Kinoshita, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Nobutaka Mukae, Fumihiko Hirai, Tetsuzo Tagawa, Yoshinao Oda, Toru Iwaki, Koji Iihara, Hiroshi Honda, Yoshihiko Maehara, Radiological features of brain metastases from non-small cell lung cancer harboring EGFR mutation, Anticancer research, 10.21873/anticanres.12653, 38, 6, 3731-3734, 2018.06, Aim: To investigate the radiological features on computed tomography (CT) of brain metastasis (BM) from epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Patients and Methods: Thirty-four patients with NSCLC with BMs who underwent surgical resection of the BMs at the Department of Neurosurgery, Kyushu University from 2005 to 2016 were enrolled in the study. The EGFR statuses of the 34 BMs were investigated. Radiological features, including the number, size, and location of the tumor, were delineated by CT. Results: Patients with EGFR-mutated BMs had significantly higher frequencies of multiple metastases than those with the non-EGFR-mutated type (p=0.042). BMs harboring mutations in EGFR were more frequently observed in the central area of the brain compared to those without mutations in EGFR (p=0.037). Conclusion: Careful follow-up of patients with EGFR-mutated NSCLC may be necessary given the high frequencies of multiple BMs and their location in the central area of the brain..
135. Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Yoshinao Oda, Yoshihiko Maehara, Significance of Spread Through Air Spaces in Resected Pathological Stage I Lung Adenocarcinoma, Annals of Thoracic Surgery, 10.1016/j.athoracsur.2018.01.037, 105, 6, 1655-1663, 2018.06, Background: “Spread through air spaces” (STAS) is a recently described invasive pattern of lung cancer that spreads within air spaces beyond the edge of the main tumor. In the current study, we investigated the significance of STAS in patients with pathologic stage I adenocarcinoma. Methods: We assessed STAS in a total of 276 patients with resected pathologic stage I adenocarcinoma. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS) using a 20x objective and a 10x ocular lens. We evaluated the association between STAS and the clinicopathologic characteristics and postoperative survivals. Results: Among 276 patients, 123 (44.6%), 48 (17.4%), and 105 (38.0%) were classified as having no, low, and high STAS, respectively. The positivity for STAS was significantly associated with larger radiologic tumor diameter (p = 0.008), higher consolidation/tumor ratio (p < 0.001), higher maximum standard uptake value (p < 0.001), pathologically larger tumor size (p = 0.004), pleural invasion (p = 0.027), and histologically invasive type (p < 0.001); whereas STAS was not significantly associated with epidermal growth factor receptor mutations or programmed death ligand-1 expression (p = 0.129 and p = 0.872, respectively). Patients with STAS had significantly shorter recurrence-free and overall survival than patients without STAS (p < 0.001 and p = 0.002, respectively). According to a multivariate analysis, positivity for STAS remained an independent prognostic factor for both recurrence-free survival and overall survival. Conclusions: Spread through air spaces was associated with clinicopathologically invasive features and was predictive of worse survival..
136. Kenichiro Yahiro,Yoshihiro Matsumoto,Jun-ichi Fukushi,Ken-ichi Kawaguchi,Makoto Endo,Nokitaka Setsu,Keiichiro IIda, Suguru Fukushima,Makoto Nakagawa,Atsushi Kimura,Yoshinao Oda,Yasuharu Nakashima, Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line., Hepatology Communications, 10.1155/2018/8987568, 2018.06.
137. Shinkichi Takamori, Gouji Toyokawa, Tatsuro Okamoto, Mototsugu Shimokawa, Fumihiko Kinoshita, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Kazuki Takada, Masakazu Katsura, Fumihiko Hirai, Fumihiro Shoji, Tetsuzo Tagawa, Yoshinao Oda, Hiroshi Honda, Yoshihiko Maehara, Clinical Impact and Risk Factors for Skeletal Muscle Loss After Complete Resection of Early Non-small Cell Lung Cancer, Annals of Surgical Oncology, 10.1245/s10434-017-6328-y, 25, 5, 1229-1236, 2018.05, Background: A relationship between sarcopenia diagnosed by skeletal muscle area (SMA) and poor prognosis in cancer patients has recently been reported. This study aimed to clarify the clinical significance of postoperatively decreased SMA in patients with early non-small cell lung cancer (NSCLC). Methods: This study selected 101 patients with pathologic stage 1 NSCLC who had undergone pre- and postoperative (~ 1 year) computed tomography scans and lobectomy between 2005 and 2010 at Kyushu University Hospital. The post/pre ratio was defined as the postoperative normalized SMA (cm
2
/m
2
) at the 12th thoracic vertebra level divided by the preoperative normalized SMA. The cutoff value for the post/pre ratio was set at 0.9. Results: The study classified 31 patients (30.7%) as having decreased SMA. Poor performance status (PS) was significantly associated with decreased SMA (p = 0.048). The patients with decreased SMA had a significantly shorter disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001) than the other patients. Decreased SMA was found to be an independent prognostic factor for DFS (p = 0.010) and OS (p = 0.0072). The independent risk factors for skeletal muscle loss included poor PS (PS ≥ 1) and obstructive ventilatory impairment [forced expiratory volume (FEV) 1% < 70%]. Conclusions: Skeletal muscle loss after surgery is significantly associated with postoperative poor outcomes for patients with early NSCLC. Patients with poor PS, obstructive ventilatory impairment, or both need careful support to maintain their skeletal muscle mass. Future prospective studies may clarify whether physical activity and nutritional support improve postoperative prognosis..
138. Hanae Fujimoto, Yoriko Saito, Kenoki Ouchida, Eiryo Kawakami, Saera Fujiki, Takashi Watanabe, Rintaro Ono, Akiko Kaneko, Shinsuke Takagi, Yuho Najima, Atsushi Hijikata, Lin Cui, Takashi Ueki, Yoshinao Oda, Shohei Hori, Osamu Ohara, Masafumi Nakamura, Takashi Saito, Fumihiko Ishikawa, Deregulated mucosal immune surveillance through gut-Associated regulatory t cells and PD-1 + t cells in human colorectal cancer, Journal of Immunology, 10.4049/jimmunol.1701222, 200, 9, 3291-3303, 2018.05, Disturbed balance between immune surveillance and tolerance May lead to poor clinical outcomes in some malignancies. In paired analyses of adenocarcinoma and normal mucosa from 142 patients, we found a significant increase of the CD4/CD8 ratio and accumulation of regulatory T cells (Tregs) within the adenocarcinoma. The increased frequency of Tregs correlated with the local infiltration and extension of the tumor. There was concurrent maturation arrest, upregulation of programmed death-1 expression, and functional impairment in CD8 + T cells (CTLs) isolated from the adenocarcinoma. Adenocarcinoma-associated Tregs directly inhibit the function of normal human CTLs in vitro. With histopathological analysis, Foxp3 + Tregs were preferentially located in stroma. Concurrent transcriptome analysis of epithelial cells, stromal cells, and T cell subsets obtained from carcinomatous and normal intestinal samples from patients revealed a distinct gene expression signature in colorectal adenocarcinoma–associated Tregs, with overexpression of CCR1, CCR8, and TNFRSF9, whereas their ligands CCL4 and TNFSF9 were found upregulated in cancerous epithelium. Overexpression of WNT2 and CADM1, associated with carcinogenesis and metastasis, in cancer-associated stromal cells suggests that both cancer cells and stromal cells play important roles in the development and progression of colorectal cancer through the formation of a tumor microenvironment. The identification of CTL anergy by Tregs and the unique gene expression signature of human Tregs and stromal cells in colorectal cancer patients May facilitate the development of new therapeutics against malignancies. The Journal of Immunology, 2018, 200: 3291–3303..
139. Kensuke Tanaka, Gouji Toyokawa, Tetsuzo Tagawa, Kayo Ijichi, Naoki Haratake, Fumihiko Hirai, Yoshinao Oda, Yoshihiko Maehara, Successful treatment of growing teratoma syndrome of the lung by surgical resection
A case report and literature review, Anticancer Research, 10.21873/anticanres.12571, 38, 5, 3115-3118, 2018.05, Growing teratoma syndrome (GTS) of the lung is extremely rare, and there are very few reports on this condition. This is a case report of GTS of the lung that was successfully treated by resection. A 19-year-old man, who had been diagnosed with a testicular tumor, lung metastases and left hilar lymph node metastasis, underwent surgical resection for left testicular cancer. After orchiectomy and chemotherapy, the patient was successfully treated with wedge resection of the right upper lobe and left upper lobectomy. In conclusion, the current case suggests that some patients with GTS might be successfully treated by surgical resection..
140. Kenichi Kawaguchi, Katsumi Harimaya, Yoshihiro Matsumoto, Mitsumasa Hayashida, Seiji Okada, Keiichiro Iida, Go Kato, Kuniyoshi Tsuchiya, Toshio Doi, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima, Effect of cartilaginous endplates on extruded disc resorption in lumbar disc herniation, PloS one, 10.1371/journal.pone.0195946, 13, 4, 2018.04, Objective The aim of this study was to investigate the clinicopathologic features of lumbar disc herniation (LDH) with endplate degeneration and the association between cartilaginous fragments and inflammatory response to the herniated disc. Summary of background data LDH often involves hyaline cartilage fragments pulled from the vertebral endplates. Modic changes are closely associated with LDH that contains hyaline cartilage, and cartilaginous endplates seem to affect resorption of the herniated disc. Methods A total of 78 patients who underwent microscopic discectomy between 9 and 16 weeks after an occurrence of LDH were reviewed. Modic changes, disc degeneration, high-intensity zone, and vertebral corner defect were evaluated using magnetic resonance imaging (MRI). Histopathological observations of cartilaginous endplates and inflamed granulation tissue in the herniated disc were made. In cases with inflamed granulation tissue, neovascularization and macrophage infiltration were also evaluated using immunohistochemical analysis. Results Modic changes were observed in approximately one-third of the patients (26 cases: type 1, 7; type 2, 17; and type 3, 2). Cartilaginous endplates were observed in 32 cases (41%) and in the majority of cases with Modic changes compared with cases without Modic changes (65%, p = 0.001). Although inflamed granulation tissue was observed in 60 cases (77%), no significant differences were detected in patient age and the composition of the herniated material. Immunohistochemical analysis showed that fewer CD34-positive capillaries and CD68-positive cells were found in cases with cartilaginous fragments compared with those without cartilaginous fragments (p < 0.001). In addition, a higher immunoreactivity to CD34 and CD68 was found in herniated discs <25% of whose area was occupied by cartilaginous endplates compared with discs whose area was occupied at 25% or more (p < 0.001). Conclusion There is an association between LDH with endplate degeneration and cartilaginous herniation, with Modic type 2 predominating. Furthermore, neovascularization and macrophage infiltration, especially if the amount of cartilage is high, are likely to be less frequent in cartilaginous herniation, leading to failure in the spontaneous remission of clinical symptoms..
141. Yasuhiro Haruta, Ryota Nakanishi, Tomoko Jogo, Yuichiro Nakashima, Hiroshi Saeki, Eiji Oki, Minako Fujiwara, Yoshinao Oda, Yoshihiko Maehara, Gastric cancer of "Crawling type" detected by additional gastrectomy after endoscopic submucosal resection, Anticancer Research, 10.21873/anticanres.12479, 38, 4, 2335-2338, 2018.04, “Crawling type” gastric cancer (GC) is known as a rare variant of early GCs, which is difficult to diagnose at an early stage because of low-grade nuclear atypia and a morphology mimicking intestinal metaplasia. This is a case report of a 69-year-old woman who was diagnosed with early-stage gastric cancer. She had endoscopic submucosal resection (ESD) and histologically, both horizontal and vertical margins were negative. Seven months after ESD, a new lesion of the stomach was detected by follow-up gastroscopy. Laparoscopic distal gastrectomy was performed and “crawling type” glands were observed throughout the whole area of the tumor. We should keep this variant in mind, especially when a tumor is superficial depressed or superficial flat type in the middle of the stomach. Careful observation with multiple biopsies of all mucosal layer and a re-biopsy is the key procedure for obtaining the right diagnosis. Endoscopic and histological characteristics should also be reviewed..
142. nobuko yasutake, Yoshihiro Ohishi, Kenichi Taguchi, Yuka Hiraki, Masafumi Oya, Yumi Oshiro, Mari Mine, Takeshi Iwasaki, Hidetaka Yamamoto, Kenichi Kouhashi, Kenzo Sonoda, Kiyoko Kato, Yoshinao Oda, Insulin-like growth factor II messenger RNA-binding protein-3 is an independent prognostic factor in uterine leiomyosarcoma, Histopathology, 10.1111/his.13422, 72, 5, 739-748, 2018.04, Aims: The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS). Methods and results: We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P < 0.0001), older age (P = 0.0244) and IMP3 expression (P = 0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (P < 0.0001) and IMP3 (P = 0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study. Conclusions: IMP3 expression in ULMS could be a marker of a poor prognosis..
143. Kyoko Yamashita, Kenichi Kouhashi, Yuichi Yamada, Takeaki Ishii, Yoshihiro Nishida, Hiroshi Urakawa, Ichiro Ito, Mitsuru Takahashi, Takeshi Inoue, Masafumi Ito, Yuuki Ohara, Yoshinao Oda, Shinya Toyokuni, Osteogenic differentiation in dedifferentiated liposarcoma
a study of 36 cases in comparison to the cases without ossification, Histopathology, 10.1111/his.13421, 72, 5, 729-738, 2018.04, Aims: Ossification is found occasionally in dedifferentiated liposarcoma (DDLPS). The aims of this study were to elucidate whether the formed bone tissue is usually produced by tumour cells or by reactive non-neoplastic cells, and to reveal the clinicopathological characteristics of DDLPS with ossification. Methods and results: We examined 36 cases of ossified DDLPS by comparing them to 31 cases of non-ossified DDLPS. MDM2 amplification was confirmed in osteocytes and/or osteoblastic cells in all but one ossified DDLPS cases (27 of 28) using fluorescence in-situ hybridisation, although the morphological impression of ossification appeared to be mainly metaplastic (27 of 36) or high-grade osteosarcoma-like (six of 36). The bone tissue was often formed predominantly at the periphery of the DDLPS area near the well-differentiated liposarcoma component (18 of 36), and an organised structure such as bone marrow-like differentiation was not uncommon (12 of 36). According to a modified French Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, ossified DDLPS tended to be lower grade than non-ossified DDLPS (mean grade: 1.88 and 2.15, respectively). Ossification in DDLPS was associated significantly with shorter local recurrence-free survival by multivariate analysis (P = 0.02347), but metaplastic-appearing ossification tended to be associated with longer overall survival (P = 0.1400). Conclusions: The bone tissue formed in DDLPS was mainly neoplastic regardless of its morphology and maturity, which highlighted the osteogenic differentiation of the tumour cells. DDLPS patients with osteogenic differentiation tended to suffer from earlier local recurrences, which did not necessarily lead to poor life outcomes..
144. Yasuto Yoneshima, Kayo Ijichi, Satoshi Anai, keiichi ota, Kohei Otsubo, Eiji Iwama, Kentaro Tanaka, Yoshinao Oda, Yoichi Nakanishi, Isamu Okamoto, PD-L1 expression in lung adenocarcinoma harboring EGFR mutations or ALK rearrangements, Lung Cancer, 10.1016/j.lungcan.2018.01.024, 118, 36-40, 2018.04, Objectives: Expression of programmed cell death–ligand 1 (PD-L1) has been associated with clinical outcome of programmed cell death–1 (PD-1) pathway blockade in non–small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay, the only companion diagnostic for pembrolizumab therapy, has revealed that ∼30% of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1 expression in NSCLCs with known driver oncogenes has remained unclear, however. Materials and methods: We retrospectively evaluated PD-L1 expression with the 22C3 assay in tumor tissue of 80 lung adenocarcinoma patients including 71 with EGFR mutations and 9 with ALK rearrangements, all of whom were treated with corresponding tyrosine kinase inhibitors (TKIs). Results: Of the 80 tumors analyzed, 26 (32.5%) had a PD-L1 tumor proportion score (TPS) of 1%–49% and 9 (11.3%) had a PD-L1 TPS of ≥50%; 35 (43.8%) thus had a PD-L1 TPS of ≥1%. Of the 71 tumors with EGFR mutations, 23 (32.4%) had a PD-L1 TPS of 1%–49% and 7 (9.9%) had a PD-L1 TPS of ≥50%. A PD-L1 TPS of ≥1% was not associated with any clinical characteristic examined. Progression-free survival on initial TKI treatment was significantly poorer for patients with a PD-L1 TPS of ≥1% than for those with a PD-L1 TPS of <1% (p =.016). Conclusions: A subset of patients with EGFR mutations or ALK rearrangements had a PD-L1 TPS of ≥50%. Prospective studies are thus warranted to examine the efficacy of PD-1/PD-L1 inhibitors in such patients..
145. Kotoe Takayoshi, Goro Doi, Nobuhiro Tsuruta, Tomoyasu Yoshihiro, Kenta Nio, Kenji Tsuchihashi, hiroshi ariyama, Jun Odawara, Shinji Shimoda, Kenichi Kouhashi, Yoshinao Oda, shinji itoh, Norifumi Harimoto, Yoshihiko Maehara, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Successful chemotherapeutic treatment for metastatic littoral cell angioma
A case report, Medicine (United States), 10.1097/MD.0000000000010378, 97, 15, 2018.04, Rationale:Metastatic littoral cell angioma (LCA) is extremely rare. No standard therapeutic strategy has been established, and the impact of chemotherapy has not yet been evaluated.Patient concerns:A 61-year-old woman was admitted because of bicytopenia. She had a splenectomy for LCA of the spleen 10 years earlier. Bone marrow aspiration was normal, and a computed tomography (CT) scan showed hepatomegaly with multiple liver tumors. Diagnoses:Liver biopsy samples showed macrophage-like cell infiltration in the hepatic sinusoids. Metastatic LCA was diagnosed based on immunohistochemistry, imaging tests, and the clinical course.Interventions:Immunosuppressive agents, such as prednisolone and cyclosporine, were ineffective. Next, cytotoxic agents, such as etoposide, paclitaxel, and vincristine, were administered.Outcomes:Cytotoxic agents showed a prominent effect against LCA. CT showed improvement of the hepatomegaly, and fluoro-deoxyglucose (FDG) uptake decreased markedly at a follow-up FDG- positron emission tomography (PET) scan.Lessons:Chemotherapeutic treatment based on hemophagocytic syndrome or angiosarcoma might have anti-tumor activity against metastatic LCA. Analysis of the molecular characteristics of this tumor is needed to develop better treatment options..
146. Makoto Kawamoto, Keigo Ozono, Yasuhiro Oyama, Akio Yamasaki, Yoshinao Oda, Hideya Ohnishi, The novel selective pan-TRK inhibitor ONO-7579 exhibits antitumor efficacy against human gallbladder cancer in vitro, Anticancer research, 10.21873/anticanres.12435, 38, 4, 1979-1986, 2018.04, We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors have been evaluated and their dramatic clinical activity is being shown for a variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO-7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II clinical trial for TRK-rearranged solid tumors. In this study, we evaluated the anticancer effect of ONO-7579 using GBC cells with or without KRAS mutant, NOZ, TYGBK-1. Our study showed that ONO-7579 had a suppressive effect on GBC proliferation in TYGBK-1, and on invasive potential and vascular endothelial growth factor expression in TYGBK-1 and NOZ. Our data indicated that ONO-7579 could be a promising treatment option for patients with GBC..
147. Masanobu Sato, Hidetaka Yamamoto, Yui Hatanaka, Toshimitsu Nishijima, Rina Jiromaru, Ryuji Yasumatsu, Kenichi Taguchi, Muneyuki Masuda, Takashi Nakagawa, Yoshinao Oda, Wnt/β-catenin signal alteration and its diagnostic utility in basal cell adenoma and histologically similar tumors of the salivary gland, Pathology Research and Practice, 10.1016/j.prp.2017.12.016, 214, 4, 586-592, 2018.04, Differential diagnosis among basal cell adenoma (BCA), basal cell adenocarcinoma (BCAC), adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) of the salivary gland can be challenging due to their similar histological appearance. Although frequent nuclear β-catenin expression and CTNNB1 mutations have been reported in BCA, further details of the Wnt/β-catenin signal alterations are unclear. The aim of this study was to assess the diagnostic utility of Wnt/β-catenin signal alteration in BCA and morphological mimics. We performed immunohistochemical staining for β-catenin and mutation analysis for Wnt/β-catenin-related genes (CTNNB1, APC, AXIN1 and AXIN2) in BCA (n = 34), BCAC (n = 3), ACC (n = 67) and PA (n = 31). We also analyzed ACC-specific MYB and MYBL1 gene rearrangements by fluorescence in situ hybridization (FISH). Nuclear β-catenin expression (≥3%) was present in 32/34 cases (94.1%) of BCA, and the nuclear β-catenin labeling index was significantly higher than in other tumor types (p = < 0.0001). In BCA, we found mutations in CTNNB1, APC and AXIN1 genes (41.1%, 2.9% and 8.8%, respectively). In BCAC, nuclear β-catenin expression with CTNNB1 mutation was present in 1/3 cases (33.3%). As for ACC, nuclear β-catenin expression was observed in 3/67 cases (4.4%), but all 3 cases harbored either MYB or MYBL1 gene rearrangement. The results suggest that nuclear β-catenin immunoreactivity with appropriate criteria may be helpful to distinguish BCA from histologically similar tumors. However, a minor subset of ACCs with nuclear β-catenin expression require careful diagnosis. In addition, Wnt/β-catenin signal alteration may play a role in the pathogenesis of BCA and BCAC..
148. Shotaro Korehisa, Tetsuo Ikeda, Shinji Okano, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Makoto Hashizume, Yoshihiko Maehara, A novel histological examination with dynamic three-dimensional reconstruction from multiple immunohistochemically stained sections of a PD-L1-positive colon cancer, Histopathology, 10.1111/his.13400, 72, 4, 697-703, 2018.03, Aims: Programmed cell death-ligand 1 (PD-L1) expression is observed in patients with microsatellite instability-high (MSI-H) colon cancer, which is susceptible to immune checkpoint blockade. The aim of this study was to investigate the interrelationship between PD-L1-positive cells and cytotoxic T cells, lymphatic vessels and vascular endothelium by using histological examination with the three-dimensional (3D) reconstruction of a PD-L1-positive colon cancer. Methods and results: Serial sections of MSI-H colon cancer tissue were stained with haematoxylin and eosin (H&E) and Masson trichrome stains; immunohistochemical analysis of PD-L1, CD8, D2-40 and CD31 was performed. Several 3D models of MSI-H colon cancer were reconstructed with a 3D data visualisation system. Moreover, 18 serial sections were stained with PD-L1, cytokeratin AE1/AE3, CD45, CD31, CD68 and H&E in the same case to confirm that PD-L1 was expressed on tumour cells, CD31-positive cells and macrophages in the invasive frontal region. Notably, there was a peak in the expression of PD-L1 and CD31 in the invasive frontal region. D2-40-positive cells were abundant in the overall tumour stroma, and CD8-positive cells infiltrated the tumour parenchyma. PD-L1 was expressed on tumour cells in the parenchyma and other cells in the stroma. Additional staining of 18 consecutive sections revealed that the other cells were CD68-positive and CD45-positive macrophages and CD31-positive proliferating vascular endothelial cells. Conclusions: We confirmed that PD-L1 was highly expressed in the invasive frontal region in 3D models of MSI-H colon cancer tissue. This method can be useful for accurately evaluating the localisation of immune checkpoint molecules..
149. Takaki Akamine, Kazuki Takada, Gouji Toyokawa, Fumihiko Kinoshita, Taichi Matsubara, Yuka Kozuma, Naoki Haratake, Shinkichi Takamori, Fumihiko Hirai, Tetsuzo Tagawa, Tatsuro Okamoto, Yasuto Yoneshima, Isamu Okamoto, Mototsugu Shimokawa, Yoshinao Oda, Yoichi Nakanishi, Yoshihiko Maehara, Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer
A comprehensive analysis of systemic inflammatory markers, Surgical Oncology, 10.1016/j.suronc.2018.01.002, 27, 1, 88-94, 2018.03, Objectives Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients. Therefore, here we investigated the potential association of PD-L1 expression with systemic inflammatory markers, including CRP, NLR, lymphocyte-monocyte ratio and platelet-lymphocyte ratio. Methods We retrospectively examined tumor PD-L1 expression in 508 surgically resected primary NSCLC cases by immunohistochemical analysis (cut-off value: 1%). The association of PD-L1 expression with preoperative systemic inflammatory markers was assessed by univariate and multivariate analyses. We generated a PD-L1 association score (A-score) from serum CRP level (cut-off value: 0.3 mg/dl) and smoking status to predict PD-L1 expression. Results Among the total 508 patients, 188 (37.0%) patients were positive for PD-L1 expression at the 1% cut-off value and 90 (17.5%) had elevated serum CRP level. Multivariate logistic regression revealed that PD-L1 positivity was significantly associated with advanced stage, the presence of vascular invasion and high serum CRP level (P =.0336,.0106 and 0.0018, respectively). Though not significant, smoking history tended to be associated with PD-L1 protein expression (P =.0717). There was no correlation with other inflammatory markers. Smoking history with elevated CRP level (A-score: 2) was strongly associated with PD-L1 protein expression (odds ratio: 5.18, P <.0001), while it was inversely associated with EGFR mutation (odds ratio: 0.11, P <.0001). Conclusions Our results indicate that among all systemic inflammatory markers examined, serum CRP seems to predict PD-L1 expression in patients with NSCLC however the clinical applicability is limited given the obtained area under the receiver operating characteristic curve values..
150. Hidetaka Yamamoto, Takeshi Iwasaki, Yuichi Yamada, Yoshihiro Matsumoto, Hiroshi Otsuka, Masato Yoshimoto, Kenichi Kouhashi, Kenichi Taguchi, Ryohei Yokoyama, Yasuharu Nakashima, Yoshinao Oda, Diagnostic utility of histone H3.3 G34W, G34R, and G34V mutant-specific antibodies for giant cell tumors of bone, Human Pathology, 10.1016/j.humpath.2017.11.020, 73, 41-50, 2018.03, Giant cell tumors of bone (GCTBs) are characterized by mononuclear stromal cells and osteoclast-like giant cells; up to 95% have H3F3A gene mutation. The RANKL inhibitor denosumab, when used for the treatment of GCTB, leads to histological changes such as new bone formation and giant cell depletion. Here we assessed the diagnostic utility of immunohistochemical staining with the antibodies against histone H3.3 G34W, G34R and G34V mutant proteins for GCTB and other histologically similar bone and joint lesions. H3.3 G34W, G34R and G34V expressions were detected in mononuclear stromal cells in 47/51 (92%), 1/51 (2%) and 3/51 (6%) cases of primary GCTBs, respectively, in a mutually exclusive manner. All recurrent/metastatic GCTBs (n = 14), post-denosumab GCTBs (n = 8) and secondary malignant GCTBs (n = 2) were positive for H3.3 G34W. The immunohistochemical results were essentially correlated with the H3F3A genotype determined by mutation analysis. In post-denosumab GCTBs, H3.3 G34W expression was seen in immature bone-forming cells. H3.3 G34W, G34R and G34V were negative in 121/122 cases of non-GCTB, including chondroblastoma, osteosarcoma, primary aneurysmal bone cyst and other giant cell–rich lesions. The exception was a single case of undifferentiated high-grade pleomorphic sarcoma that was positive for H3.3 G34W, suggesting the possibility of sarcomatous overgrowth of primary malignant GCTB. Therefore, H3.3 G34W/R/V mutant-specific antibodies are useful surrogate markers for the H3F3A genotype and helpful for the diagnosis of GCTB and its variants. The expression of H3.3 G34W mutant protein in post-denosumab GCTB suggests that neoplastic stromal cells may play a role in new bone formation..
151. Xiaopeng Bai, Eikichi Ihara, Katsuya Hirano, Yoshimasa Tanaka, Kayoko Nakano, Satomi Kita, Takahiro Iwamoto, Haruei Ogino, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura, Yoshihiro Ogawa, Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger, CMGH Cellular and Molecular Gastroenterology and Hepatology, 10.1016/j.jcmgh.2017.11.004, 5, 3, 209-221, 2018.03, Background and Aims: Hydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. Methods: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H2S to LES contractility was investigated by examining the effects of inhibitors of H2S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function. Results: Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp–induced relaxation was accompanied by a decrease in [Ca2+]i and inversely correlated with the extracellular Na+ concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+ exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic mice compared with wild-type mice. Conclusions: Endogenous H2S regulates the LES myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia..
152. Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Fumihiko Kinoshita, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Fumihiko Hirai, Yoshinao Oda, Yoshihiko Maehara, High frequency of spread through air spaces in resected small cell lung cancer, Anticancer Research, 10.21873/anticanres.12421, 38, 3, 1821-1825, 2018.03, Background/Aim: Spread through air spaces (STAS) is a novel invasive pattern of lung cancer, especially adenocarcinoma and squamous cell carcinoma. However, its frequency and significance in patients with resected small cell lung cancer (SCLC) remains unclear. Patients and Methods: A total of 30 patients with resected SCLC were analyzed for STAS. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS). We evaluated the association between STAS and clinicopathological characteristics and postoperative survivals. Results: Among 30 patients, 5 (17%), 6 (20%) and 19 (63%) were classified as having no, low and high STAS, respectively. Fisher’s exact test demonstrated no significant associations between the positivity for STAS and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survival between STAS-negative/low and STAS-high patients. Conclusion: STAS was frequently observed in patients with resected SCLC..
153. Hiroshi Otsuka, Kenichi Kouhashi, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuichi Yamada, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda, Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors, Pathology Research and Practice, 10.1016/j.prp.2017.12.015, 214, 3, 417-425, 2018.03, The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs. We evaluated immunohistochemical expression of H3K27me3 in MPNSTs with heterologous components and metachronous cases of MPNSTs. Among 145 MPNST samples, 50 (34.5%) showed complete loss of staining, and 45 (31.0%) showed partial loss of staining. Regarding the backgrounds of MPNSTs, 43 patients of neurofibromatosis type 1 (NF-1)-associated MPNST demonstrated 19 (44.2%) complete and 12 (27.9%) partial loss of H3K27me3. Among MPNSTs with heterologous component, almost all of MPNSTs with epithelioid differentiation (8/9 samples, 88.9%) retained H3K27me3, and malignant Triton tumors without epithelioid component lacked H3K27me3 at high rate (91.7%). Five of 20 metachronous MPNST cases showed significantly reduced expression of H3K27me3 between primary and later-occurring tumors, but in some cases increased expression of H3K27me3 in the clinical course (such as complete loss to partial loss) was observed. If the tumors are recurrent or metastatic, H3K27me3 expression should be reduced or at least maintained because loss of H3K27me3 is due to genetic mutation of EED or SUZ12. MPNSTs, especially those associated with NF-1, can occur in heterochronous and multiple patterns, and the identification of increased expression of H3K27me3 during a patient's clinical course can be helpful for determining whether the tumors are heterochronous, multiple or not. As heterochronous and multiple tumors may show lower malignancy compared to recurrent or metastatic tumors, favorable prognosis may be expected when H3K27me3 expression is increased..
154. Shotaro Korehisa, Tetsuo Ikeda, Shinji Okano, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Makoto Hashizume, Yoshihiko Maehara, A novel histological examination with dynamic three-dimensional reconstruction from multiple immunohistochemically stained sections of a PD-L1-positive colon cancer, Histopathology, 10.1111/his.13400, 72, 4, 697-703, 2018.03, Aims: Programmed cell death-ligand 1 (PD-L1) expression is observed in patients with microsatellite instability-high (MSI-H) colon cancer, which is susceptible to immune checkpoint blockade. The aim of this study was to investigate the interrelationship between PD-L1-positive cells and cytotoxic T cells, lymphatic vessels and vascular endothelium by using histological examination with the three-dimensional (3D) reconstruction of a PD-L1-positive colon cancer. Methods and results: Serial sections of MSI-H colon cancer tissue were stained with haematoxylin and eosin (H&E) and Masson trichrome stains; immunohistochemical analysis of PD-L1, CD8, D2-40 and CD31 was performed. Several 3D models of MSI-H colon cancer were reconstructed with a 3D data visualisation system. Moreover, 18 serial sections were stained with PD-L1, cytokeratin AE1/AE3, CD45, CD31, CD68 and H&E in the same case to confirm that PD-L1 was expressed on tumour cells, CD31-positive cells and macrophages in the invasive frontal region. Notably, there was a peak in the expression of PD-L1 and CD31 in the invasive frontal region. D2-40-positive cells were abundant in the overall tumour stroma, and CD8-positive cells infiltrated the tumour parenchyma. PD-L1 was expressed on tumour cells in the parenchyma and other cells in the stroma. Additional staining of 18 consecutive sections revealed that the other cells were CD68-positive and CD45-positive macrophages and CD31-positive proliferating vascular endothelial cells. Conclusions: We confirmed that PD-L1 was highly expressed in the invasive frontal region in 3D models of MSI-H colon cancer tissue. This method can be useful for accurately evaluating the localisation of immune checkpoint molecules..
155. Jorge Guzman‐Lepe, Eduardo Cervantes‐Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M. Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J. Fox, Kazuki Takeishi, Alejandro Soto‐Gutierrez, Liver-enriched transcription factor expression relates to chronic hepatic failure in humans, Hepatology Communications, 0.1002/hep4.1172., 2018.03.
156. Shotaro Korehisa, Eiji Oki, Makoto Iimori, Yu Nakaji, Mototsugu Shimokawa, Hiroshi Saeki, Shinji Okano, Yoshinao Oda, Yoshihiko Maehara, Clinical significance of programmed cell death-ligand 1 expression and the immune microenvironment at the invasive front of colorectal cancers with high microsatellite instability, International Journal of Cancer, 10.1002/ijc.31107, 142, 4, 822-832, 2018.02, Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI-H); however, the specific cell types that respond to immune checkpoint therapy are unclear. Herein, we aimed to examine the expression of programmed cell death-ligand 1 (PD-L1) and related proteins in MSI-H and microsatellite-stable (MSS) CRCs to investigate the immune microenvironment at the tumor's invasive front. The MSI status was retrospectively assessed in 499 patients undergoing surgical resection of primary CRC; of these, 48 were classified as MSI-H. Propensity score matching was performed, and tissues from 36 and 37 patients with MSI-H and MSS CRCs, respectively, were immunohistochemically evaluated for PD-L1, PD-1, CD8 and CD68. PD-L1 expression was evaluated separately for tumor cells (PD-L1 [T]) and tumor-infiltrating myeloid cells in the stroma (PD-L1 [I]). PD-L1 (T) was positive in only 5.4% and 36.1% of MSS and MSI-H CRCs, while PD-L1 (I) was positive in 27% and 72.2% of these CRCs, respectively. The PD-L1 (T) and PD-L1 (I) expression levels in MSI-H CRCs significantly correlated with poor differentiation, lymphatic invasion and vascular invasion (p < 0.05), and with early-stage adenocarcinoma and high budding grade (p < 0.05), respectively. Significantly more PD-L1 (I), CD8-positive cells and CD68-positive macrophages were present at the invasive front than in the central tumor in MSI-H CRCs (p < 0.005). PD-L1 was expressed on both tumor cells and CD68/CD163-positive (M2) macrophages at the invasive front of MSI-H CRCs. In conclusion, PD-L1-positive tumor cells and M2-type tumor-associated macrophages may contribute to tumor invasion and immune escape at the invasive front..
157. Yuichi Yamada, Izumi Kinoshita, Kohashi Kenichi, Hidetaka Yamamoto, Takeshi Iwasaki, Hiroshi Otsuka, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuki Kuma, Nokitaka Setsu, Yuki Koga, Yumi Honda, Takeshi Inoue, Hiroyuki Yanai, Kyoko Yamashita, Ichiro Ito, Mitsuru Takahashi, Shouichi Ohga, Masutaka Furue, Yasuharu Nakashima, Yoshinao Oda, Histopathological and genetic review of phosphaturic mesenchymal tumours, mixed connective tissue variant, Histopathology, 10.1111/his.13377, 72, 3, 460-471, 2018.02, Aims: Phosphaturic mesenchymal tumour, mixed connective tissue variant (PMT-MCT), is a tumour of uncertain differentiation, characterised by ‘smudgy/grungy’ calcification and vitamin D-resistant phosphaturic osteomalacia. Fibroblast growth factor (FGF)23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation has never been performed. We reviewed cases of tumour-associated osteomalacia or histologically definitive PMT-MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings. Methods and results: A total of 19 tumours from 14 cases diagnosed previously as PMT-MCT were retrieved, on which immunohistochemical staining, reverse transcription–polymerase chain reaction (RT–PCR) and fluorescence in-situ hybridisation (FISH) analysis were performed. Histologically, fibrous capsule, calcification and giant cell reaction tended to be observed in soft-tissue PMT-MCT, while PMT-MCT of bone and multiple PMT-MCT showed an infiltrative growth pattern. The immunohistochemical results were as follows: the tumour cells were positive for FGF23 (nine of 12, 75%), FGFR1 (11 of 11, 100%), CD56 (12 of 14, 85.7%) and E26 oncogene homologue (ERG) (5 of 13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in seven of 14 formalin-fixed paraffin-embedded (FFPE) specimens and all five frozen specimens by RT–PCR. The level of FGF23 mRNA, which was determined by real-time PCR, varied among the phosphaturic cases. Two of 17 tumours were positive for FGFR1 gene rearrangement. Conclusions: It was considered that PMT-MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without fibronectin 1 (FN1)–FGFR1 fusion gene. The authors propose that the histology of PMT-MCT differs depending on its location, such as bone or soft tissue, which could complicate the differential diagnosis..
158. Fumihiko Kinoshita, Fumihiro Shoji, Kazuki Takada, Gouji Toyokawa, Tatsuro Okamoto, Tokujiro Yano, Yoshinao Oda, Yoshihiko Maehara, Mucinous adenocarcinoma of the thymus
report of a case, General Thoracic and Cardiovascular Surgery, 10.1007/s11748-017-0781-1, 66, 2, 111-115, 2018.02, Thymic mucinous adenocarcinoma is a very rare neoplasm. This tumor has a poor prognosis and its treatment is not established. In addition, the existence of KRAS mutations of thymic mucinous adenocarcinoma is still unknown, despite these mutations are common in lung mucinous adenocarcinoma. We present the case of a 79-year-old woman with primary thymic mucinous adenocarcinoma. Therefore, we reviewed clinico-pathological features of thymic mucinous adenocarcinoma in details and analyzed KRAS gene mutations of the present case..
159. Kazuki Takada, Gouji Toyokawa, Tetsuzo Tagawa, Kenichi Kouhashi, Mototsugu Shimokawa, Takaki Akamine, Shinkichi Takamori, Fumihiko Hirai, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara, PD-L1 expression according to the EGFR status in primary lung adenocarcinoma, Lung Cancer, 10.1016/j.lungcan.2017.12.003, 116, 1-6, 2018.02, Objectives It was reported that programmed cell death-ligand 1 (PD-L1) expression is associated with smoking and wild-type epidermal growth factor receptor (EGFR) in lung adenocarcinoma. However, the association between PD-L1 expression and EGFR mutation site in EGFR mutation-positive lung adenocarcinoma is unclear. Materials and methods We retrospectively examined the relationship between PD-L1 expression and EGFR status in 441 surgically resected primary lung adenocarcinomas. Membrane PD-L1 expression on tumor cells was evaluated by immunohistochemical analysis using a PD-L1 antibody (clone SP142) and defined by tumor proportion scores (TPSs) of 0%, 1–4%, 5–49%, and ≥50%, respectively. Results Two hundred and eighteen (49.4%) patients had wild-type EGFR, and 223 (50.6%) had mutant EGFR—98 (44.0%) with exon 19 deletion, 116 (52.0%) with exon 21 L858R point mutation, and nine (4.0%) with another EGFR mutation. Overall, Fisher's exact test showed that PD-L1 positivity was associated with wild-type EGFR, and there was only one case with PD-L1 TPS ≥50% among the cases with mutant EGFR. The analysis of cases with mutant EGFR indicated no significant association between EGFR mutation site and PD-L1 expression. However, the prevalence of PD-L1 TPS 5–49% was higher among patients with EGFR exon 19 deletion than with EGFR exon 21 L858R point mutation. Conclusions PD-L1 expression was significantly associated with wild-type EGFR, and PD-L1 TPS ≥50% seldom overlaps with presence of driver oncogene EGFR. There was no significant difference in PD-L1 expression among the EGFR mutation sites.
160. Shinji Kohsaka, Tsuyoshi Saito, Keisuke Akaike, Yoshiyuki Suehara, Takuo Hayashi, Tatsuya Takagi, Kazuo Kaneko, Toshihide Ueno, Shinya Kojima, Kenichi Kouhashi, Hiroyuki Mano, Yoshinao Oda, Takashi Yao, Pediatric soft tissue tumor of the upper arm with LMNA-NTRK1 fusion, Human Pathology, 10.1016/j.humpath.2017.08.017, 72, 167-173, 2018.02, A 6-year-old girl was admitted to our hospital because of the presence of a slow-growing tumor in her right elbow. Biopsy specimens showed a round to spindle cell neoplasm with uncertain malignant potential, leading to the decision of surgical resection. Histologically, the resected tumor was encapsulated by fibrous tissue but focally invaded the surrounding skeletal muscles. The tumor was composed of ganglion cell–like short spindle cells with lymphocytic infiltration in the collagenous background. Tumor cells with large bizarre nuclei were occasionally observed, and multinucleated giant cells were scattered at the periphery. Hemangiopericytoma-like patterns and adipose tissue elements were not evident, and mitotic figures were rarely observed (<1 per 10 high-power fields). Immunohistochemically, the tumor cells were positive for S-100 and CD34 and focally positive for epithelial membrane antigen and AE1/AE3. RNA sequencing and subsequent reverse-transcription polymerase chain reaction revealed alternative splicing forms of LMNA-NTRK1 fusion (Ex2-Ex10 and Ex2-Ex15)..
161. Naoki Haratake, Gouji Toyokawa, Kazuki Takada, Yuka Kozuma, Taichi Matsubara, Shinkichi Takamori, Takaki Akamine, Masakazu Katsura, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara, Programmed Death-Ligand 1 Expression and EGFR Mutations in Multifocal Lung Cancer, Annals of Thoracic Surgery, 10.1016/j.athoracsur.2017.09.025, 105, 2, 448-454, 2018.02, Background Little is known about the programmed death-ligand 1 (PD-L1) expression in multifocal lung cancer, such as the expression in multiple primary lung cancer and pulmonary metastasis. In this translational study, we investigated PD-L1 expression and its relationship with the epidermal growth factor receptor (EGFR) mutation status in resected multifocal lung cancer. Methods The PD-L1 expression in 152 samples of multifocal lung cancer from 59 patients was evaluated by an immunohistochemical analysis. Results Among the 152 lung cancer lesions of 59 patients, PD-L1 expression was observed in 29 lesions (19.1%) of 20 patients (33.9%). Among 43 patients with 112 multiple primary lung cancer lesions, 15 lesions (13.4%) of 13 patients (30.2%) were PD-L1 positive; and among 16 patients with 40 pulmonary metastatic lesions, 14 lesions (35.0%) of 7 patients (43.8%) were PD-L1-positive. Among 43 patients with multiple primary lung cancer, there was disagreement of PD-L1 expression in 12 patients (27.9%, κ = 0.104). On the contrary, among 16 patients with pulmonary metastasis, disagreement of PD-L1 expression was observed only in 1 patient (6.3%, κ = 0.871). In pulmonary metastatic lesions, the frequency of PD-L1 positivity among lesions with wild-type EGFR was significantly higher than among lesions with mutated EGFR (66.7% versus 0%: p < 0.001). Conclusions This study provides important evidence of higher levels of agreement of PD-L1 expression in pulmonary metastasis compared with in multiple primary lung cancer, and high positivity of PD-L1 expression in pulmonary metastatic lesions with wild-type EGFR in an Asian population..
162. Yae Kanai, Hiroshi Nishihara, Yohei Miyagi, Tatsuhiro Tsuruyama, Kenichi Taguchi, Hiroto Katoh, Tomoyo Takeuchi, Masahiro Gotoh, Junko Kuramoto, Eri Arai, Hidenori Ojima, Ayako Shibuya, Teruhiko Yoshida, Toshiaki Akahane, Rika Kasajima, Kei Ichi Morita, Johji Inazawa, Takeshi Sasaki, Masashi Fukayama, Yoshinao Oda, The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research
Standard operating procedures based on empirical analyses, Pathology International, 10.1111/pin.12631, 68, 2, 63-90, 2018.02, Genome research using appropriately collected pathological tissue samples is expected to yield breakthroughs in the development of biomarkers and identification of therapeutic targets for diseases such as cancers. In this connection, the Japanese Society of Pathology (JSP) has developed “The JSP Guidelines on the Handling of Pathological Tissue Samples for Genomic Research” based on an abundance of data from empirical analyses of tissue samples collected and stored under various conditions. Tissue samples should be collected from appropriate sites within surgically resected specimens, without disturbing the features on which pathological diagnosis is based, while avoiding bleeding or necrotic foci. They should be collected as soon as possible after resection: at the latest within about 3 h of storage at 4°C. Preferably, snap-frozen samples should be stored in liquid nitrogen (about −180°C) until use. When intending to use genomic DNA extracted from formalin-fixed paraffin-embedded tissue, 10% neutral buffered formalin should be used. Insufficient fixation and overfixation must both be avoided. We hope that pathologists, clinicians, clinical laboratory technicians and biobank operators will come to master the handling of pathological tissue samples based on the standard operating procedures in these Guidelines to yield results that will assist in the realization of genomic medicine..
163. Kenzo Sonoda, Hideaki Yahata, Okugawa Kaoru, Kaneki Eisuke, Tatsuhiro Ogami, Masafumi Yasunaga, Shingo Baba, Yoshinao Oda, Hiroshi Honda, Kiyoko Kato, Value of Intraoperative Cytological and Pathological Sentinel Lymph Node Diagnosis in Fertility-Sparing Trachelectomy for Early-Stage Cervical Cancer, Oncology, 10.1159/000484049, 94, 2, 92-98, 2018.02, Background and Objectives: Trachelectomy, a fertility-sparing surgery for early-stage cervical cancer, can be performed only when there is no extrauterine extension present. Therefore, identifying the sentinel lymph nodes (SLNs) and using them to obtain an intraoperative pathologic diagnosis can provide information on the feasibility and safety of trachelectomy. Our aim was to assess the value of an intraoperative SLN diagnosis. Methods: We retrospectively analyzed the accuracy of intraoperative imprint cytology and frozen-section examination in 201 patients at our institution in whom trachelectomy was planned. Results: All patients could be evaluated for SLNs; a total of 610 SLNs were analyzed. Although the specificity of both imprint cytology and frozen-section examination was 100.0%, the sensitivity was only 58.6 and 65.5%, respectively. The diagnostic sensitivity was higher in 2-mm slices along the short axis than on bisection along the longitudinal axis. Imprint cytology correctly diagnosed 2 patients who had false-negative results on frozen section. The nature of the metastatic foci that caused an intraoperative false-negative diagnosis was either micrometastasis or isolated tumor cells. Conclusions: The accuracy of intraoperative SLN diagnosis requires improvement, especially when small metastatic foci are present..
164. Kenjiro Date, Takao Ohtsuka, So Nakamura, Naoki Mochidome, Yasuhisa Mori, Yoshihiro Miyasaka, Yoshinao Oda, Masafumi Nakamura, Surveillance of patients with intraductal papillary mucinous neoplasm with and without pancreatectomy with special reference to the incidence of concomitant pancreatic ductal adenocarcinoma, Surgery (United States), 10.1016/j.surg.2017.09.040, 163, 2, 291-299, 2018.02, Background: The presence of an intraductal papillary mucinous neoplasm is important in the detection of concomitant pancreatic ductal adenocarcinoma. The aim of this study was to elucidate the incidence and timing of development of concomitant pancreatic ductal adenocarcinoma in patients with and without pancreatectomy for intraductal papillary mucinous neoplasm. Methods: We reviewed retrospectively the surveillance data for 22 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm (pancreatic ductal adenocarcinoma-resection group), 180 who underwent pancreatectomy for intraductal papillary mucinous neoplasm (intraductal papillary mucinous neoplasm-resection group), and 263 whose intraductal papillary mucinous neoplasms were left untreated (nonresection group). The incidence and timing of the development of a concomitant pancreatic ductal adenocarcinoma during the surveillance of patients with and without partial pancreatectomy for intraductal papillary mucinous neoplasm were investigated using the Kaplan-Meier method. Results: During a median surveillance period of 40 months (range 6–262 months), 5 patients in the pancreatic ductal adenocarcinoma-resection group, 6 in the intraductal papillary mucinous neoplasm-resection group, and 8 in the nonresection group developed concomitant pancreatic ductal adenocarcinoma. The estimated 5-year (17%) and 10-year (56%) cumulative incidences of secondary pancreatic ductal adenocarcinoma in the pancreatic ductal adenocarcinoma-resection group were significantly greater than those in the other two groups (P <.01). Conversely, the difference in the estimated cumulative incidence of concomitant pancreatic ductal adenocarcinoma between the intraductal papillary mucinous neoplasm-resection and nonresection groups was not significant (5-year, 5.0% vs 2.2%; 10-year, 5.0% vs 8.7%; P =.87). Conclusion: Long-term (≥5-year) surveillance in patients with intraductal papillary mucinous neoplasm is necessary and important because of the potential for development of concomitant pancreatic ductal adenocarcinoma. Those with a history of resection of concomitant pancreatic ductal adenocarcinoma at the time of the initial operation are at quite high risk for the development of secondary pancreatic ductal adenocarcinoma..
165. Yoshiaki Kinoshita, Tomoyuki Hida, Makoto Hamasaki, Shinji Matsumoto, Ayuko Sato, Tohru Tsujimura, Kunimitsu Kawahara, Kenzo Hiroshima, Yoshinao Oda, Kazuki Nabeshima, A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma, Cancer cytopathology, 10.1002/cncy.21928, 126, 1, 54-63, 2018.01, BACKGROUND: Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The authors previously described that IHC expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM tissues. In the current study, the authors investigated whether a combination of MTAP and BAP1 IHC could distinguish MPM from reactive mesothelial cells (RMC) in cell blocks obtained from pleural effusions. METHODS: The authors examined IHC expression of MTAP and BAP1 in cell blocks obtained from pleural effusions of 45 cases of MPM and 21 cases of reactive mesothelial hyperplasia. Furthermore, IHC expression of MTAP was compared with the deletion status of 9p21 FISH. RESULTS: MTAP and BAP1 IHC differentiated MPM from RMC with 100% specificity for both and sensitivities of 42.2% and 60.0%, respectively. The combination of MTAP and BAP1 IHC yielded a sensitivity of 77.8%, which was higher than that of BAP1 IHC alone or 9p21 FISH alone (62.2%). Moreover, a high degree of concordance was observed between the results of MTAP IHC and 9p21 FISH in cell blocks. CONCLUSIONS: A combination of MTAP and BAP1 IHC in cell blocks from pleural effusions appears to be a reliable and useful method for differentiating MPM cells from RMC and can be used in the routine diagnosis of MPM. Cancer Cytopathol 2018;126:54–63..
166. Yasuki Hijikata, Toshihiko Okazaki, Yoshihiro Tanaka, Mutsunori Murahashi, Yuichi Yamada, Kazunari Yamada, Atsushi Takahashi, Hiroyuki Inoue, Junji Kishimoto, Yoichi Nakanishi, Yoshinao Oda, Yusuke Nakamura, Kenzaburo Tani, A phase I clinical trial of RNF43 peptide-related immune cell therapy combined with low-dose cyclophosphamide in patients with advanced solid tumors, PLoS One, 10.1371/journal.pone.0187878, 13, 1, 2018.01, The objective of this study was to investigate the safety and the tolerability of combined cellular immunotherapy with low-dose cyclophosphamide (CPA) in patients with advanced solid tumors. This study targeted a novel tumor-associated antigen, ring finger protein 43 (RNF43). Eligible patients were resistant to standard therapy, HLA-A*24:02- or A*02:01positive and exhibiting high RNF43 expression in their tumor cells. They were administered 300 mg/m2 CPA followed by autologous lymphocytes, preliminarily cultured with autologous RNF43 peptide-pulsed dendritic cells (DCs), RNF43 peptide-pulsed DCs and systemic low dose interleukin-2. The primary endpoint was safety whereas the secondary endpoint was immunological and clinical response to treatment. Ten patients, in total, were enrolled in this trial. Primarily, no adverse events greater than Grade 3 were observed. Six out of 10 patients showed stable disease (SD) on day 49, while 4 other patients showed progressive disease. In addition, one patient with SD exhibited a partial response after the second trial. The frequency of regulatory T cells (Tregs) in patients with SD significantly decreased after CPA administration. The ratio of interferon-γ-producing, tumor-reactive CD8+ T cells increased with time in patients with SD. We successfully showed that the combination of immune cell therapy and CPA was safe, might induce tumor-specific immune responses and clinical efficacy, and was accompanied by a decreased ratio of Tregs in patients with RNF43-positive advanced solid tumors..
167. Hironori Mikumo, Toyoshi Yanagihara, Naoki Hamada, Mikiko Hashisako, Kayo Ijichi, Kunihiro Suzuki, Eiji Harada, Yasunori Shikada, Yoshinao Oda, Yoichi Nakanishi, An autopsy case of bird-related chronic hypersensitivity pneumonitis presenting with repeated acute exacerbation, Respiratory Medicine Case Reports, 10.1016/j.rmcr.2018.04.016, 24, 92-94, 2018.01, A 68-year-old woman was admitted to our hospital with a dry cough in 2010. Chest computed tomography showed the appearance of a nonspecific interstitial pneumonia (NSIP) pattern. Video-assisted thoracoscopic surgery (VATS) was performed, and the specimens prominently showed a usual interstitial pneumonia (UIP) pattern. She was diagnosed with bird-related chronic hypersensitivity pneumonitis (BRCHP) on the basis of the detection of antibodies to pigeon dropping extract in her serum and a history of using feather-filled duvets and indirect exposure to birds in her living environment. Even though she was treated with corticosteroids and immunosuppressants and recommended to avoid bird-related antigens, she had a progressive course with repeated acute exacerbation episodes and died of respiratory failure. The autopsy findings showed diffuse alveolar damage superimposed on UIP. Clinicians should be aware that BRCHP patients especially with histopathologically UIP pattern may experience acute exacerbation..
168. Kunio Iura, Kenichi Kouhashi, Nobuko Yasutake, Takeaki Ishii, Akira Maekawa, Hirofumi Bekki, Hiroshi Otsuka, Yuichi Yamada, Hidetaka Yamamoto, Yoshihiro Ohishi, Yoshihiro Matsumoto, Yukihide Iwamoto, Yoshinao Oda, Cancer-testis antigens are predominantly expressed in uterine leiomyosarcoma compared with non-uterine leiomyosarcoma, Oncology Letters, 10.3892/ol.2017.7274, 15, 1, 441-446, 2018.01, Leiomyosarcomas account for ~24% of all adult sarcomas, and develop predominantly either in the uterus [uterine leiomyosarcoma (ULMS)] or in deep soft tissue or the retroperitoneum [non-uterine leiomyosarcoma (NULMS)]. Leiomyosarcomas are relatively chemoresistant tumors, and the prognosis of patients with leiomyosarcomas is poor. Cancer-testis (CT) antigens are considered promising immunotherapeutic targets because of their restricted expression in normal tissue, except in the testis. Little is known about the expression of CT antigens in leiomyosarcomas. In the present study, the protein expression of the CT antigens MAGE family member A (MAGEA)1, MAGEA3, MAGEA4, G antigen 7 (GAGE7) and cancer/testis antigen 1 (NY-ESO-1) in ULMS and NULMS were investigated using immunohistochemistry (IHC), and their expression profiles compared. In ULMS and NULMS, positive expression was observed in 11/32 (31%) and 1/31 (3%; MAGEA1), 15/32 (47%) and 5/31 (16%; MAGEA3), 11/32 (34%) and 3/31 (10%; MAGEA4), 23/32 (72%) and 11/31 (35%; GAGE7) and 3/32 (9%) and 0/31 (0%; NY-ESO-1), respectively. The ULMSs demonstrated significantly higher positive expression of MAGEA1 (P=0.0034), MAGEA3 (P=0.0141), MAGEA4 (P=0.0319) and GAGE7 (P=0.0054) compared with the NULMSs. The ULMSs also had significantly higher IHC scores for MAGEA1 (P=0.0023), MAGEA3 (P=0.0474), MAGEA4 (P=0.011), GAGE7 (P=0.0319) and NY-ESO-1 (P=0.0437). The results of the present study support the potential utility of MAGEA1, MAGEA3, MAGEA4 and GAGE7 in ULMS and GAGE7 in NULMS as immunotherapeutic targets..
169. Shinkichi Takamori, Gouji Toyokawa, Isamu Okamoto, Kazuki Takada, Fumihiko Kinoshita, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Nobutaka Mukae, Fumihiko Hirai, Tetsuzo Tagawa, Yoshinao Oda, Toru Iwaki, Koji Iihara, Yoichi Nakanishi, Yoshihiko Maehara, Clinical significance of PD-L1 expression in brain metastases from non-small cell lung cancer, Anticancer Research, 10.21873/anticanres.12258, 38, 1, 553-557, 2018.01, Aim: To investigate the association between positivity for programmed cell death-ligand 1 (PD-L1) in brain metastases (BM) and the prognosis or clinical factors in patients with non-small cell lung cancer (NSCLC). Materials and Methods: Thirty-two patients with surgically resected brain-metastatic NSCLC were enrolled. The PD-L1 expression in BM was analyzed using the antibody against human PD-L1 (clone SP142). The PD-L1 positivity was defined as PD-L1 expression on brain-metastatic tumor cells of =5%. Results: Seven (21.9%) out of 32 patients showed PD-L1 positivity in BM. The PD-L1-positive BM group had a significantly shorter brain-specific disease-free survival than the PD-L1-negative BM group (p<0.05). PD-L1 positivity in BM was significantly associated with a heavy smoking history and the administration of radiotherapy for BM before surgery (p<0.05 and p<0.05, respectively). Conclusion: The PD-L1 expression in BM from NSCLC may be associated with local recurrence following surgery, and the smoking- or radiotherapy-derived effects..
170. Kayoko Nakano, Hidetaka Yamamoto, Minako Fujiwara, Yutaka Koga, Shinichi Tsuruta, Eikichi Ihara, Eiji Oki, Masafumi Nakamura, Yoshihiro Ogawa, Yoshinao Oda, Clinicopathologic and molecular characteristics of synchronous colorectal carcinoma with mismatch repair deficiency, American Journal of Surgical Pathology, 10.1097/PAS.0000000000000947, 42, 2, 172-182, 2018.01, Synchronous colorectal carcinoma (CRC) is a unique disease associated with a high prevalence (∼35%) of microsatellite instability and occasionally with Lynch syndrome. The clinicopathologic and molecular features of synchronous CRC are poorly understood, particularly in Japanese patients. We examined 118 Japanese patients (236 tumors) with synchronous CRC and 117 Japanese patients (117 tumors) with solitary CRC with immunohistochemical staining for TP53 and mismatch repair (MMR) protein (MLH1, MSH2, PMS2, and MSH6) and mutation analyses of KRAS and BRAF genes. The results revealed no significant differences in clinicopathologic, histologic, and molecular findings between the synchronous and solitary CRC groups. Among the 118 synchronous CRC patients, 15 (12.7%) showed loss of MMR protein(s) expression in at least 1 tumor, whereas 103 (87.3%) showed intact expression of all 4 MMR proteins in both tumors. Of note, all patients with MMR deficiency had excellent prognoses. The 15 patients were further subdivided into 2 groups: the Concordant group, with concordant MMR loss (n=9, 7.6%) and the Discordant group, with discordant MMR loss (n=6, 5.1%). The Concordant patients showed concurrent MLH1/PMS2 loss (n=3), concurrent MSH2/ MSH6 loss (n=4) and isolated MSH6 loss (n=2) in both tumors, whereas the Discordant patients showed concurrent MLH1/PMS2 loss (n=2), isolated PMS2 loss (n=2) and isolated MSH6 loss (n=2) in a single tumor. On the basis of the MMR expression pattern and BRAF mutation, the Concordant and Discordant groups were suspected to include Lynch syndrome, Lynch-like syndrome and sporadic MLH1 promoter hypermethylated CRC. In addition, KRAS mutation was present in only 1 tumor in a single patient in each group. In conclusion, the frequency of MMR protein deficiency in synchronous CRC in the Japanese population may be lower compared with the reported data from Western populations. MMR protein loss and KRAS and BRAF mutations in synchronous CRCs were heterogenous even in an individual patient..
171. Masakazu Katsura, Fumihiro Shoji, Tatsuro Okamoto, Shinichiro Shimamatsu, Fumihiko Hirai, Gouji Toyokawa, Yosuke Morodomi, Tetsuzo Tagawa, Yoshinao Oda, Yoshihiko Maehara, Correlation between CXCR4/CXCR7/CXCL12 chemokine axis expression and prognosis in lymph-node-positive lung cancer patients, Cancer Science, 10.1111/cas.13422, 109, 1, 154-165, 2018.01, The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of tumor cells during cancer development by modulating site-specific distant metastasis including to regional lymph nodes. We investigated the correlation of these chemokine expressions to prognosis in lymph-node-positive non-small-cell lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar and/or mediastinal lymph nodes (N1-2) were collected. CXCR4, CXCR7 and CXCL12 expressions were evaluated. Cox regression analysis was performed to determine whether these chemokines were independent prognostic factors in N1-2 NSCLC. High expression of CXCR4 in PS and CXCL12 in MLN was associated with poor overall survival (OS) (P =.025 and.033, respectively). Significant correlations between CXCR4 expression in PS and CXCL12 expression in MLN were observed (P =.040). There was significant difference in OS between 2 groups according to expressions of CXCR4 in PS and CXCL12 in MLN (P =.0033). Expression of CXCL12 in MLN was identified as an independent prognostic factor (HR 1.79, 95% CI 1.08-3.04, P =.023). CXCL12 in MLN was mainly expressed by tumor cells compared with stromal cells (56% vs 25%, respectively, P <.0001). CXCR4/CXCL12 may play roles in tumor progression in MLN and is associated with poor prognosis of lymph-node-positive NSCLC patients..
172. Takeo Fujino, Shujiro Inoue, Shunsuke Katsuki, Taiki Higo, Tomomi Ide, Yoshinao Oda, Hiroyuki Tsutsui, Fatal cardiac hemochromatosis in a patient with hereditary spherocytosis, International Heart Journal, 10.1536/ihj.17-160, 59, 2, 427-430, 2018.01, A 31-year-old man was admitted to our hospital with atrial tachycardia and cardiogenic shock. He had been diagnosed with hereditary spherocytosis (HS) during childhood, but he never received any red blood cell transfusions. Right ventricular endomyocardial biopsy revealed multiple myocardial hemosiderin deposits, and he was diagnosed with cardiac hemochromatosis. In addition to the iron deposition in the heart, the loss of myocyte and severe interstitial fibrosis were present. His cardiac function did not improve even after the cardioversion for atrial tachycardia, and he suffered from recurrent heart failure. Despite intensive medical treatment for heart failure and arrhythmias in combination with iron chelation therapy, he eventually died of progressive and refractory heart failure. Hemochromatosis is a systemic disorder characterized by the excessive deposition of iron in multiple organs. The occurrence of hemochromatosis in HS is extremely rare, and previous reports have shown that the coexistence of heterozygosity for the HFE gene mutation in HS patients causes excess iron storage. The prognosis is poor due to progressive congestive heart failure and refractory arrhythmias. Here we report a rare case of fatal cardiac hemochromatosis associated with HS. The possibility of cardiac hemochromatosis needs to be considered in cases of heart failure or arrhythmia in patients with HS..
173. Ohtsuka Takao, Yasuhisa Mori, Takaaki Fujimoto, Yoshihiro Miyasaka, Kohei Nakata, Kenoki Ouchida, Eishi Nagai, Yoshinao Oda, Shuji Shimizu, Masafumi Nakamura, Feasibility of prophylactic pancreatojejunostomy in possible high-risk patients for prevention of pancreatic fistula during enucleation or limited pancreatic resection, American Surgeon, 84, 1, 149-153, 2018.01, The aim of this study was to assess the feasibility of prophylactic pancreatojejunostomy after enucleation or limited pancreatic resection regarding the risk of postoperative pancreatic fistula (PF). We retrospectively reviewed the medical records of 32 patients who underwent enucleation or limited pancreatic resection and compared the clinical parameters between patients with (n 5 10) and without (n 5 22) prophylactic pancreatojejunostomy. Prophylactic pancreatojejunostomy was performed in patients with a possible high risk ofPF. No operation-related mortality occurred. Operation time was significantly longer (P < 0.01) and blood loss significantly greater (P < 0.01) in patients with pancreatojejunostomy. Overall complications were more frequent (P 5 0.02) and postoperative hospital stay was significantly longer (P 5 0.02) in patients with pancreatojejunostomy. However, other assessed factors including the prevalence of postoperative PF did not differ between groups. In conclusion, prophylactic pancreatojejunostomy is feasible, and its efficacy in preventing PF after enucleation or limited pancreatic resection in high-risk patients will require further study..
174. Tetsuko Kobayashi, Yuhki Koga, masataka ishimura, Kentaro Nakashima, Wakako Kato, Hiroaki Ono, Motoshi Sonoda, Katsuhide Eguchi, Reiji Fukano, Satoshi Honjo, Yoshinao Oda, Shoichi Ohga, Fever and skin involvement at diagnosis predicting the intractable langerhans cell histiocytosis
40 case-series in a single center, Journal of Pediatric Hematology/Oncology, 10.1097/MPH.0000000000001080, 40, 3, e148-e153, 2018.01, Langerhans cell histiocytosis (LCH) occurs as a clonal disease with enigmatic immune responses. LCH patients occasionally present with fever, although the significance remains elusive. We investigated the predicting factors for developing intractable disease of refractory and/or reactivated LCH. In total, 40 pediatric LCH patients managed in Kyushu University from 1998 to 2014 were enrolled. The medical records were analyzed retrospectively. Sixteen patients suffered from multisystem (MS) LCH involving risk organs (ROs) (n=4) or not (n=12). In total, 24 patients had single-system LCH affecting bone (multi n=8, single n=13), skin (n=2), or lymph node lesions (n=1). Eight patients had the intractable disease of 7 MS or 1 multibone LCH. Two patients died from MS LCH with or without RO involvement. Ten patients showed persistent fever (>38°C) at onset. Intractable cases had fever, RO and skin involvement, leukocytosis, coagulopathy, microcytic anemia, higher levels of soluble interleukin-2 receptor and C-reactive protein, more frequently at diagnosis. Multivariate analysis indicated that fever and skin lesions at diagnosis were independently associated with the intractability (odds ratio: fever, 35.5; 95% confidence interval, 3.0-1229.1; skin lesions, 24.6; 95% confidence interval, 1.9-868.7). Initial fever and skin involvement might predict the development of intractable and fatal-risk LCH even without the RO involvement..
175. Norifumi Harimoto, K. Yugawa, Toru Ikegami, M. Ohira, Yohei Mano, T. Motomura, Takeo Toshima, shinji itoh, N. Harada, Yuji Soejima, Tomoharu Yoshizumi, Yoshihiko Maehara, Yoshinao Oda, Hepatobiliary and Pancreatic
Pregnancy induced hepatic veno-occlusive disease requiring liver transplantation, Journal of Gastroenterology and Hepatology (Australia), 10.1111/jgh.13975, 33, 1, 2018.01.
176. Toyoshi Yanagihara, Norio Yamamoto, Yasuaki Kotetsu, Naoki Hamada, Eiji Harada, Kunihiro Suzuki, Kayo Ijichi, Yoshinao Oda, Yoichi Nakanishi, Interstitial pneumonia caused by dabigatran, Respiratory Medicine Case Reports, 10.1016/j.rmcr.2017.10.009, 23, 10-12, 2018.01, We describe the case of a 73-year-old man who experienced dry cough and exertional dyspnea after dabigatran administration. Chest radiographs revealed the development of bilateral consolidative and ground glass opacity, and transbronchial lung biopsy showed organized materials in the alveolar spaces with moderate inflammatory infiltrate and focal fibrosis. Lung opacity gradually disappeared after discontinuing dabigatran. To date, there has been only one report regarding dabigatran-induced lung injury, except for alveolar hemorrhage and eosinophilic pneumonia. Therefore, we should consider that any drug can cause various types of lung injuries..
177. Mohammed Yahia Farrag Aly, Yasuhisa Mori, Yoshihiro Miyasaka, Ohtsuka Takao, Yoshihiko Sadakari, Kohei Nakata, Yoshinao Oda, Shuji Shimizu, Masafumi Nakamura, Laparoscopic surgery for congenital biliary dilatation
a single-institution experience, Surgery Today, 10.1007/s00595-017-1545-3, 48, 1, 44-50, 2018.01, Purpose: Laparoscopic surgery as a treatment for congenital biliary dilatation is uncommon. We herein present a series of laparoscopic surgeries for congenital biliary dilatation performed in our institution and review our experience with this approach over a long period of time. Methods: Medical records of 36 consecutive patients who underwent laparoscopic surgery for congenital biliary dilatation from 1996 to 2015 were retrospectively reviewed. Data on patient demographics, operative time, blood loss, hospital stay, and complications were evaluated. A comparison between the former period (Group A, 1996–2005) and the latter period (Group B, 2006–2015) was performed. Results: The patients comprised 23 females and 13 males with a median age of 34 years. The median operative time, blood loss, and hospital stay was 493 min, 154 g, and 11 days, respectively. Total early and late complications occurred in 7 (19%) and 2 (5%) patients, respectively. A comparison between Groups A and B revealed no significant difference in operative time or complications, but operative blood loss, open conversion, and hospital stay were significantly lower in Group B than in Group A (P < 0.05). Conclusion: Laparoscopic surgery for congenital biliary dilatation is feasible and provides acceptable results. Further prospective studies of larger numbers of patients are needed..
178. Ohtsuka Takao, Yoshitaka Gotoh, Yohei Nakashima, Yoshifumi Okayama, So Nakamura, Makiko Morita, Mohammed Yahia Farrag Aly, Vittoria Vanessa D.M. Velasquez, Yasuhisa Mori, Yoshihiko Sadakari, Kohei Nakata, Yoshihiro Miyasaka, Kosei Ishigami, Nao Fujimori, Naoki Mochidome, Yoshinao Oda, Shuji Shimizu, Masafumi Nakamura, Role of SpyGlass-DStm in the preoperative assessment of pancreatic intraductal papillary mucinous neoplasm involving the main pancreatic duct, Pancreatology, 10.1016/j.pan.2018.04.012, 2018.01, Background/Objectives: It is often difficult to determine an adequate resection line during pancreatectomy for intraductal papillary mucinous neoplasm involving the main pancreatic duct during partial pancreatectomy. The aim of this study was to evaluate the usefulness of improved peroral pancreatoscopy using SpyGlass-DStm in the preoperative assessment of intraductal papillary mucinous neoplasm involving the main pancreatic duct. Methods: We collected and retrospectively analyzed clinicopathological data from seven consecutive patients who underwent preoperative assessment of intraductal papillary mucinous neoplasm involving the main duct using SpyGlass-DStm. Results: Good imaging quality of the intraductal protruding lesion was obtained in all seven patients, and only one adverse event was noted wherein a patient had mild pancreatitis. Six patients underwent pancreatectomy. In one patient, masked-type concomitant pancreatic ductal adenocarcinoma and low-length dysplastic lesion was found near the surgical margin, which was not detected by preoperative imaging modalities including SpyGlass-DStm. The sensitivity of targeting biopsy during SpyGlass-DStm to diagnose high-grade dysplasia was 0%. Conclusions: SpyGlass-DStm can be safely performed in patients with intraductal papillary mucinous neoplasm involving the main duct, and has excellent visualization of the target lesion. However, challenges include poor diagnostic ability of targeting biopsy, and, therefore, intraoperative frozen section is still needed to obtain negative surgical margins..
179. Kenichi Kouhashi, Hidetaka Yamamoto, Yuichi Yamada, Izumi Kinoshita, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda, SWI/SNF Chromatin-remodeling Complex Status in SMARCB1/INI1-preserved Epithelioid Sarcoma, American Journal of Surgical Pathology, 10.1097/PAS.0000000000001011, 42, 3, 312-318, 2018.01, The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits such as SMARCB1/INI1 (INI1), SMARCA4/BRG1 (BRG1), SMARCC1/BAF155 (BAF155), and SMARCC2/BAF170 (BAF170), can be viewed as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. Epithelioid sarcoma, which classified as a tumor of uncertain differentiation, shows an almost complete loss of INI1. However, some cases of epithelioid sarcoma have preserved INI1, and the clinicopathologic features of these cases are uncertain. To date, there has been no investigation focused on the SWI/SNF chromatin-remodeling complex in INI1-preserved epithelioid sarcoma cases. First, an investigation of INI1 immunoexpression statuses in 60 formalin-fixed paraffin-embedded epithelioid sarcoma specimens (proximal type, 29 cases; conventional type, 31 cases) was performed. In the available INI1-preserved epithelioid sarcoma cases, we analyzed the BRG1, BAF155, and BAF170 protein expressions. INI1 preservation was observed in 6 of 29 (21%) proximal-type and 2 of 31 (6%) conventional-type epithelioid sarcoma cases. Six cases of INI1-preserved epithelioid sarcomas of proximal type were available for further immunohistochemical study. One proximal type showed loss of BAF170, and 2 proximal-type cases revealed loss of BRG1 with preservation of the other remaining core subunit proteins. One proximal-type case showed a mosaic pattern of BRG1 and loss of BAF155. However, in the remaining 2 proximal-type cases, all core subunit proteins were preserved. Overall, these results suggest that loss of expression of SWI/SNF chromatin-remodeling complex proteins has an important role in tumorigenesis. The remaining 2 INI1-preserved epithelioid sarcoma cases may have had other abnormalities causing dysfunction of SWI/SNF chromatin remodeling..
180. Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Fumihiko Kinoshita, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Fumihiko Hirai, Yoshinao Oda, Yoshihiko Maehara, Significance of Spread Through Air Spaces in Resected Lung Adenocarcinomas With Lymph Node Metastasis, Clinical Lung Cancer, 10.1016/j.cllc.2018.04.002, 2018.01, To clarify the prognostic impact of spread through air spaces (STAS) on survival in completely resected adenocarcinomas with lymph node metastasis, we observed STAS in 45 (73.0%) of 63 patients. Those with STAS had a significantly shorter recurrence-free survival (RFS) than those without STAS (P =.04). Positivity for STAS was an independent prognostic parameter for RFS. Background: Spread through air spaces (STAS) is a recently recognized invasive pattern of lung cancer defined by the World Health Organization as micropapillary clusters, solid nests, or single cells spreading within air spaces beyond the edge of the main tumor. Although STAS has been shown to be a significant prognosticator for the postoperative survival in early-stage lung cancer treated with limited resection, its prognostic impact on the survival in completely resected adenocarcinomas with lymph node metastasis remains unclear. Patients and Methods: STAS was assessed in a total of 63 adenocarcinomas with lymph node metastasis in patients who underwent complete resection. STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. We evaluated the association between STAS and the clinicopathologic characteristics and the postoperative survival. Results: Among 63 patients, 31 (49.2%) and 32 (50.8%) had disease that was pathologically positive for N1 and N2, respectively. STAS was observed in 45 patients (73.0%) and was not significantly associated with any clinicopathologic characteristics. Patients with the STAS had significantly shorter recurrence-free survival (RFS) but not overall survival than those without STAS (P =.04 and P =.35, respectively). The 5-year RFS in patients with and without STAS was 25.1% and 56.7%, respectively. According to a multivariate analysis, positivity for STAS remained an independent prognostic parameter for RFS (hazard ratio = 3.09; 95% confidence interval, 1.47-7.16; P <.01). Conclusion: STAS was predictive of a poor RFS in completely resected adenocarcinomas with lymph node metastasis..
181. Atsushi Abe, Yoshihiro Ohishi, Tetsuyuki Miyazaki, Keigo Ozono, Naoki Mochidome, Kiyoshi Saeki, Masafumi Nakamura, Yoshinao Oda, ‘Microcystic pattern’ should be recognised as part of the morphological spectrum of solid-pseudopapillary neoplasm of the pancreas, Histopathology, 10.1111/his.13376, 72, 2, 216-226, 2018.01, Aim: Solid pseudopapillary neoplasm (SPN) is an uncommon pancreatic tumour characterised by solid and pseudopapillary growth patterns. We have observed SPNs can show a microcystic pattern (microcystic SPN), which has been poorly described and may be confused with microcystic neoplasms. We conducted the present study to clarify the clinicopathological and immunohistochemical features of microcystic SPNs. Methods and results: We examined a consecutive series of 44 SPNs and 10 serous cystadenomas (SCAs), and classified them into 13 microcystic SPNs (29.5%) and 31 conventional SPNs (70.5%). Clinicopathological analysis, immunohistochemical staining and mucin histochemistry were performed. Clear cell change, hyalinised stroma and haemorrhage were observed significantly more frequently in the microcystic SPNs compared to the conventional SPNs. Immunohistochemically, the microcystic SPNs showed significantly lower frequencies of CD10 (0%) and CD56 expression (62%) compared to the conventional SPNs (87%; P < 0.001, 90%; P < 0.0085, respectively). There were no significant differences in other clinicopathological and immunohistochemical features between the two groups (i.e. the nuclear expression of β-catenin, E-cadherin, progesterone receptor (PgR), lack of forkhead box (Fox)L2 and occasional oestrogen receptor (ER), AE1/AE3 expression). Microcystic SCAs lack such a characteristic immunophenotype. The myxoid stroma of microcystic SPNs contained hyaluronan revealed by Alcian blue stain with hyaluronidase digestion. Conclusion: We thus conclude that the microcystic pattern should be recognised as a part of the morphological spectrum of SPNs. Our findings may contribute to the correct diagnosis of the pancreatic neoplasms with the microcystic pattern. In addition, we speculate that stromal change caused by an accumulation of hyaluronan may contribute to the microcystic pattern of SPN..
182. Iura K, Kohashi K, Yasutake N, Ishii T, Maekawa A, Bekki H, Otsuka H, Yamada Y, Yamamoto H, Ohishi Y, Matsumoto Y, Iwamoto Y, Oda Y. , Cancer‑testis antigens are predominantly expressed in uterine leiomyosarcoma compared with non‑uterine leiomyosarcoma. 
, ONCOLOGY LETTERS , 10.3892/ol.2017.7274, 15, 1, 441-446, 15(1):441-446, 2018.01.
183. Tomoyo Matsuda, Yuko Haraguchi, Satoko Shibata-Kikuchi, Fumiyoshi Fushimi, Yuichi Yamada, Yoshinao Oda, Masutaka Furue, A case of solitary fibrous tumor, Nishinihon Journal of Dermatology, 10.2336/nishinihonhifu.80.450, 80, 5, 450-454, 2018.01, A 35-year-old Japanese female visited us complaining of a soft subcutaneous tumor on her hip. Physical examination revealed a cystic lesion measuring 40×35 mm with a mosaic echo pattern and a rich blood flow. We surgically removed it. Histopathologically, the tumor showed a patternless architecture with branching hemangiopericytoma-like vessels. The tumor cells were immunoreactive for CD34 and STAT-6. This tumor had a NAB2-STAT6 gene fusion as determined by reverse transcription polymerase chain reaction. We diagnosed this case as a solitary fibrous tumor (SFT). SFTs are known as pleural mesenchymal neoplasms. Extrapleural SFTs are uncommon, but they may be found in various organs including the meninges, subcutaneous tissue, and soft tissue of the extremities. NAB2-STAT6 fusion genes are specific for SFTs and the detection of the fusion gene can be helpful for diagnosis. Recently, the use of immunohistochemistry for STAT-6 as a surrogate for detecting the fusion gene has been reported. SFTs are uncommon subcutaneous soft tissue tumors and should be differentiated from other spindle cell-type mesenchymal neoplasms by the detection of a NAB2-STAT6 fusion gene or immunohistochemical positivity for STAT-6..
184. Minako Inoue, Ken Okamura, Chie Kitaoka, Fumio Kinoshita, Ryo Namitome, Udai Nakamura, Masaki Shiota, Kenichi Goto, Toshio Ohtsubo, Kiyoshi Matsumura, Yoshinao Oda, Masatoshi Eto, Takanari Kitazono, Metyrapone-responsive ectopic acth-secreting pheochromocytoma with a vicious cycle via a glucocorticoid-driven positive-feedback mechanism, Endocrine Journal, 10.1507/endocrj.EJ18-0025, 65, 7, 755-767, 2018.01, In ectopic ACTH-secreting pheochromocytoma, combined ACTH-driven hypercortisolemia and hypercatecholaminemia are serious conditions, which can be fatal if not diagnosed and managed appropriately, especially when glucocorticoid-driven positive feedback is suggested with a high ACTH/cortisol ratio. A 46-year-old man presented with headache, rapid weight loss, hyperhidrosis, severe hypertension and hyperglycemia without typical Cushingoid appearance. Endocrinological examinations demonstrated elevated plasma and urine catecholamines, serum cortisol and plasma ACTH. Moreover, his ACTH/cortisol ratio and catecholamine levels were extremely high, suggesting catecholamine-dominant ACTH-secreting pheochromocytoma. Computed tomography revealed a large right adrenal tumor.18F-FDG positron emission tomography showed uptake in the area of the adrenal tumor, while123I-metaiodobenzylguanidine scintigraphy showed no accumulation. His plasma ACTH level paradoxically became elevated after a dexamethasone suppression test. After metyrapone administration, not only serum cortisol but also plasma ACTH levels were exponentially decreased almost in parallel, suggesting a glucocorticoid-driven positive-feedback regulation in this rapidly exacerbated ectopic ACTH-producing pheochromocytoma. Interestingly enough, plasma catecholamine levels were also decreased by metyrapone, although they remained extremely high. He became severely dehydrated due to hypoadrenalism requiring hydrocortisone supplementation. His clinical signs and symptoms were improved, and right adrenalectomy was performed uneventfully, resulting in complete remission of pheochromocytoma and Cushing’s syndrome. A glucocorticoid-driven positive-feedback regulation in this ectopic ACTH-secreting pheochromocytoma created a vicious cycle with rapid exacerbation of both hypercortisolemia and hypercatecholaminemia with extremely elevated plasma ACTH level. Metyrapone was clinically effective to stop this vicious cycle; nonetheless, great care must be taken to avoid hypoadrenalism especially when hypercatecholaminemia remained..
185. Yuki Kuma, Yuichi Yamada, Hidetaka Yamamoto, Kenichi Kouhashi, Takamichi Ito, Masutaka Furue, Yoshinao Oda, A novel fusion gene CRTC3-MAML2 in hidradenoma
histopathological significance, Human Pathology, 10.1016/j.humpath.2017.10.004, 70, 55-61, 2017.12, Hidradenoma usually presents as a solitary, slow-growing, and solid or cystic nodular lesion, which arises in various anatomical sites. Its diagnosis is occasionally difficult because the tumor shares histological features with other cutaneous appendage tumors. Recently, CRTC1-MAML2 fusion gene was reported in hidradenomas, with the fusion transcript being demonstrated in approximately 50% of cases. However, limited information is available regarding its clinical significance. Here, we investigated the relationship between the fusion gene and clinicohistopathological features. We reviewed 39 cases histologically diagnosed as hidradenoma. Reverse-transcription polymerase chain reaction (RT-PCR) was performed for all 39 cases, and fluorescence in situ hybridization was also performed for the RT-PCR–negative cases. The 39 tumors included 36 clear cell hidradenomas and 3 poroid hidradenomas. The details of the cellular components were as follows: clear cell–dominant type, 9 cases; polygonal cell–dominant type, 21 cases; and equally mixed type, 9 cases. There were no tumors with apparent mucinous cells. There were 8 tumors with prominent cystic change, 2 of which presented apocrine-like decapitated secretion. CRTC1-MAML2 fusion was detected in 10 of the 39 tumors (26%) and CRTC3-MAML2 fusion in 2 of the 39 (5%) by RT-PCR. MAML2 gene rearrangement was detected in 11 of 27 fusion gene–negative cases by fluorescence in situ hybridization. Moreover, neither the fusion genes nor gene rearrangement was detected in prominent cystic tumors and poroid hidradenomas. We conclude that CRTC1/3-MAML2 fusion gene analysis can be a useful method for diagnosing hidradenoma. Considering the histological and genetic similarity to mucoepidermoid carcinoma, hidradenoma may be a cutaneous counterpart of salivary gland mucoepidermoid carcinoma..
186. Kazuki Takada, Gouji Toyokawa, Tetsuzo Tagawa, Kenichi Kouhashi, Takaki Akamine, Shinkichi Takamori, Fumihiko Hirai, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara, Association Between PD-L1 Expression and Metabolic Activity on 18F-FDG PET/CT in Patients with Small-sized Lung Cancer, Anticancer Research, 37, 12, 7073-7082, 2017.12, AIM: We evaluated the metabolic characteristics of small-sized lung cancer using 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) with regard to programmed cell death ligand 1 (PD-L1) expression.
MATERIALS AND METHODS: PD-L1 expression was evaluated by immunohistochemistry with the antibody clone SP142 in 263 patients with surgically resected primary small-sized lung cancer. Specimens with <5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 expression and the maximum standardized uptake value (SUVmax) in preoperative 18F-FDG PET/CT.
RESULTS: Among patients with non-small cell lung cancer (NSCLC), the SUVmax was significantly higher in those with PD-L1 expression than in those without (p<0.0001). However, there was no correlation between SUVmax and PD-L1 expression in patients with neuroendocrine tumors (p=0.9638). Multivariate analysis revealed that smoking and a high SUVmax were independent predictors of PD-L1 expression.
CONCLUSION: PD-L1 expression was related to high glucose metabolism in small-sized NSCLC..
187. Masayo Yoshimura, Yoshiaki Kinoshita, Makoto Hamasaki, Shinji Matsumoto, Tomoyuki Hida, Yoshinao Oda, Kazuki Nabeshima, Diagnostic application of BAP1 immunohistochemistry to differentiate pleural mesothelioma from metastatic pleural tumours, Histopathology, 10.1111/his.13321, 71, 6, 1011-1014, 2017.12.
188. Daisuke Tsurumaru, mitsutoshi miyasaka, Toshio Muraki, Akihiro Nishie, Yoshiki Asayama, Eiji Oki, Yoshinao Oda, Hiroshi Honda, Histopathologic diversity of gastric cancers
Relationship between enhancement pattern on dynamic contrast-enhanced CT and histological type, European Journal of Radiology, 10.1016/j.ejrad.2017.10.018, 97, 90-95, 2017.12, Purpose To evaluate the diagnostic value of contrast-enhanced computed tomography gastrography (CE-CTG) to predict the histological type of gastric cancer. Materials and methods We analyzed 47 consecutive patients with resectable advanced gastric cancer preoperatively evaluated by multiphasic dynamic contrast-enhanced CT. Two radiologists independently reviewed the CT images and they determined the peak enhancement phase, and then measured the CT attenuation value of the gastric lesion for each phase. The histological types of gastric cancers were assigned to three groups as differentiated-type, undifferentiated-type, and mixed-type. We compared the peak enhancement phase of the three types and compared the CT attenuation values in each phase. Results The peak enhancement was significantly different between the three types of gastric cancers for both readers (reader 1, p = 0.001; reader 2, p = 0.009); most of the undifferentiated types had peak enhancement in the delayed phase. The CT attenuation values of undifferentiated type were significantly higher than those of differentiated or mixed type in the delayed phase according to both readers (reader 1, p = 0.002; reader 2, p = 0.004). Conclusion CE-CTG could provide helpful information in diagnosing the histological type of gastric cancers preoperatively..
189. Yusuke Yanagi, Koichi Nakayama, Tomoaki Taguchi, Shin Enosawa, Tadashi Tamura, Koichiro Yoshimaru, Toshiharu Matsuura, Makoto Hayashida, Kenichi Kouhashi, Yoshinao Oda, Takayoshi Yamaza, Eiji Kobayashi, In vivo and ex vivo methods of growing a liver bud through tissue connection, Scientific Reports, 10.1038/s41598-017-14542-2, 7, 1, 2017.12, Cell-based therapy has been proposed as an alternative to orthotopic liver transplantation. The novel transplantation of an in vitro-generated liver bud might have therapeutic potential. In vivo and ex vivo methods for growing a liver bud are essential for paving the way for the clinical translation of liver bud transplantation. We herein report a novel transplantation method for liver buds that are grown in vivo involving orthotopic transplantation on the transected parenchyma of the liver, which showed long engraftment and marked growth in comparison to heterotopic transplantation. Furthermore, this study demonstrates a method for rapidly fabricating scalable liver-like tissue by fusing hundreds of liver bud-like spheroids using a 3D bioprinter. Its system to fix the shape of the 3D tissue with the needle-array system enabled the fabrication of elaborate geometry and the immediate execution of culture circulation after 3D printing-thereby avoiding an ischemic environment ex vivo. The ex vivo-fabricated human liver-like tissue exhibited self-tissue organization ex vivo and engraftment on the liver of nude rats. These achievements conclusively show both in vivo and ex vivo methods for growing in vitro-generated liver buds. These methods provide a new approach for in vitro-generated liver organoids transplantation..
190. Eiji Oki, Shinji Okano, Hiroshi Saeki, Yuichiro Umemoto, Koji Teraishi, Yu Nakaji, Kouji Andou, Yoko Zaitsu, Nami Yamashita, Masahiko Sugiyama, Yuichiro Nakashima, Kippei Ohgaki, Yoshinao Oda, Yoshihiko Maehara, Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma, Oncology, 10.1159/000479231, 93, 6, 387-394, 2017.12, Objectives: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. Materials and Methods: We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients. RNA interference was used to downregulate HER2 expression, and PD-L1 protein expression was assessed by flow cytometry using the gastric cancer cell line MKN45. Results: Overexpression of PD-L1 was significantly correlated with tumor invasion (p = 0.011) and associated with poor survival. The number of PD-L1-positive cases increased according to the HER2 score in clinical samples. siRNA-mediated downregulation of HER2 significantly decreased PD-L1 protein expression in MKN45 cells. Conclusions: PD-L1 expression was associated with poor survival of gastric cancer, and HER2 signaling affects the expression of PD-L1 in gastric cancer. In gastric cancer, PTEN and HER2 are potential candidate biomarkers for developing human antibodies that block PD-L1..
191. Satoshi Kuwamoto, Michiko Matsushita, Kenichi Takeda, Natsumi Tanaka, Yukari Endo, Akira Yamasaki, Kenichi Kouhashi, Yoshinao Oda, Yasushi Horie, SMARCA4-deficient thoracic sarcoma
report of a case and insights into how to reach the diagnosis using limited samples and resources, Human Pathology, 10.1016/j.humpath.2017.05.024, 70, 92-97, 2017.12, SMARCA4-deficient thoracic sarcoma is a recently proposed new entity of soft tissue sarcomas with an undifferentiated round cell morphology that is diagnostically challenging. Here we report a case of this tumor where the diagnosis was established using limited samples and resources. A woman in her early 30s developed two intrathoracic masses. Biopsies for these lesions showed sheets of undifferentiated round/rhabdoid cells that retained SMARCB1 expression. Further analysis revealed a reduced SMARCA4 expression and a complete loss of SMARCA2 expression in tumor cells. Subsequent Sanger sequencing identified a nonsense c.1546A>T (p.516Lys>Ter) mutation in SMARCA4 and confirmed the diagnosis. Our case highlighted clinicopathological correlation and rational use of tissue sections for immunohistochemistry may enable to diagnose this tumor even when only limited samples are available. Recognition of this new entity is important for further understanding of the disease and the future development of specific therapies..
192. Keigo Ozono, Yoshihiro Ohishi, Hideya Ohnishi, Katsuya Nakamura, Junichi Motoshita, Masato Kato, Ryoichi Nakanishi, Masafumi Nakamura, Yoshinao Oda, Brain-derived neurotrophic factor/tropomyosin-related kinase B signaling pathway contributes to the aggressive behavior of lung squamous cell carcinoma, Laboratory Investigation, 10.1038/labinvest.2017.45, 97, 11, 1332-1342, 2017.11, The tropomyosin-related kinase (Trk) family consists of TrkA, TrkB, and TrkC, which play essential roles in tumor progression and/or suppression in various cancers. Little is known about the biological significance of the Trk family in human lung squamous cell carcinoma (SCC). Here we investigated the clinical significance of the protein expression of Trk family members in samples from 99 SCC patients, and we explored the relationship between invasion/proliferation activities and Trk expression using lung SCC cell lines to clarify the biological significance of the Trk family in lung SCC. Immunohistochemical high expression of TrkB was significantly correlated with vascular invasion (P=0.004), lymph node metastasis (P<0.001), and advanced stage (P=0.0015). The overall survival of the patients with TrkB-high expression was significantly shorter than those with TrkB-low expression (P=0.0110). TrkA/TrkC expressions were not predictors of poor prognosis. An in vitro assay demonstrated that the inhibition of brain-derived neurotrophic factor (BDNF) (a TrkB ligand) and TrkB by K252a (a Trk inhibitor) or siRNA (BDNF-siRNA, TrkB-siRNA) suppressed the invasion, migration, and proliferative activities of lung SCC cells. The administration of recombinant human BDNF (rhBDNF) enhanced the invasion, migration, and proliferation activities, which were abrogated by K252a. TrkB-siRNA transfection increased the protein expression of E-cadherin and decreased vimentin expressions in lung SCC cells. Matrix metalloproteinase-2 (MMP-2)-mediated gelatin degradations were decreased in lung SCC cells transfected with TrkB-siRNA. Thus, TrkB-high expression is an indicator of poor prognosis in lung SCC, probably due to invasion/proliferation activities promoted by the BDNF/TrkB signaling pathway, which could become a therapeutic target for lung SCC..
193. Gouji Toyokawa, Kazuki Takada, Tatsuro Okamoto, Mototsugu Shimokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara, Computed Tomography Features of Lung Adenocarcinomas With Programmed Death Ligand 1 Expression, Clinical Lung Cancer, 10.1016/j.cllc.2017.03.008, 18, 6, e375-e383, 2017.11, Our objective was to clarify the computed tomography features of programmed death-ligand 1 (PD-L1)–expressing lung adenocarcinomas. Among 394 patients, 78 (19.8%) were positive for PD-L1 expression. On multivariate analysis, the presence of convergence (P <.01) and cavitation (P <.01) and the absence of surrounding ground glass opacity (P =.02) and air bronchogram (P =.03) were shown to be significantly associated with PD-L1 expression. Introduction The development of immune checkpoint inhibitors against programmed death 1 has paved the way for a new era of treatment of lung cancer. Programmed death-ligand 1 (PD-L1) is expected to predict the response of immune checkpoint inhibitors in lung cancer. Predicting PD-L1 expression using a noninvasive method before immunotherapy would, therefore, help identify patients for whom immunotherapy can be successful. Patients and Methods A total of 394 patients with resected lung adenocarcinoma who had undergone preoperative thin-section computed tomography (CT) were analyzed for PD-L1 expression by immunohistochemistry and evaluated to determine the association between PD-L1 expression and CT characteristics, including convergence, surrounding ground glass opacity (GGO), air bronchogram, notching, pleural indentation, spiculation, and cavitation. Results Of the 394 patients, 78 (19.8%) were positive and 316 (80.2%) were negative for PD-L1 expression. Univariate analysis demonstrated that PD-L1+ adenocarcinoma was significantly associated with the presence of convergence (P <.01), notching (P <.01), spiculation (P <.01), and cavitation (P <.01) and the absence of surrounding GGO (P <.01) compared with PD-L1 cases. On multivariate analysis, the presence of convergence (P <.01) and cavitation (P <.01) and the absence of surrounding GGO (P =.02) and air bronchogram (P =.03) were significantly associated with PD-L1 expression. Conclusion PD-L1+ adenocarcinoma cases showed convergence and cavitation more frequently than did PD-L1 cases. In contrast, surrounding GGO and air bronchogram were observed less frequently in PD-L1+ cases than in PD-L1 cases. These results will prove helpful in identifying PD-L1–expressing adenocarcinoma by CT before immunotherapy..
194. Tomoyasu Yoshihiro, Kenji Tsuchihashi, Kenta Nio, Shuji Arita, Takafumi Nakano, Ryuji Yasumatsu, Rina Jiroumaru, hiroshi ariyama, Hitoshi Kusaba, Yoshinao Oda, Koichi Akashi, Eishi Baba, Lingual alveolar soft part sarcoma responsive to pazopanib
A case report, Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries, 10.1097/MD.0000000000008470, 96, 44, e8470, 2017.11, RATIONALE: The multi-targeted tyrosine kinase inhibitors such as cediranib, sunitinib and pazopanib have been reported to be effective for alveolar soft part sarcoma (ASPS). The efficacy of pazopanib for the patient with lingual ASPS has yet to be reported.
PATIENT CONCERNS: A 23-year old man presented with articulation disorder and swelling of the tongue. Diagnosis of lingual ASPS was made after incisional biopsy and complete excision of the mass was performed. Three months later, he presented with a protruding mental region.
DIAGNOSES: Computed tomography revealed mental region mass and lung metastasis.
INTERVENTIONS: After the failure of combination therapy of doxorubicin and ifosfamide, pazopanib was administered.
OUTCOMES: Shrinkage of both the mental region and lung mass continued for more than two months, but regrowth was confirmed at the fourth month.
LESSONS: Lingual ASPS is an exceedingly rare subset of ASPS with distinct molecular and histological characteristics and appropriate therapy remains to be established. Our findings suggest a possible therapeutic strategy for lingual ASPS..
195. Kazuki Takada, Gouji Toyokawa, Tatsuro Okamoto, Shingo Baba, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Hiroshi Honda, Yoshinao Oda, Yoshihiko Maehara, Metabolic characteristics of programmed cell death-ligand 1-expressing lung cancer on 18F-fluorodeoxyglucose positron emission tomography/computed tomography, Cancer Medicine, 10.1002/cam4.1215, 6, 11, 2552-2561, 2017.11, Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) with regard to PD-L1 protein expression. PD-L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative 18F-FDG PET/CT. The cut-off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD-L1 protein expression compared with those without PD-L1 protein expression (P < 0.0001). However, there was no correlation between SUVmax and PD-L1 protein expression in patients with neuroendocrine tumors (P = 0.6545). Multivariate analysis revealed that smoking, the presence of pleural invasion, and high SUVmax were independent predictors of PD-L1 positivity. PD-L1-expressing NSCLC had a high glucose metabolism. The SUVmax in preoperative 18F-FDG PET/CT was a predictor of PD-L1 protein expression in patients with NSCLC..
196. Taketo Matsunaga, Ohtsuka Takao, Koichi Asano, Hideyo Kimura, Kenoki Ouchida, Hidehisa Kitada, Noboru Ideno, Yasuhisa Mori, Shoji Tokunaga, Yoshinao Oda, Sushovan Guha, Massimo Raimondo, Masafumi Nakamura, Masao Tanaka, S100P in Duodenal Fluid Is a Useful Diagnostic Marker for Pancreatic Ductal Adenocarcinoma, Pancreas, 10.1097/MPA.0000000000000940, 46, 10, 1288-1295, 2017.11, Objectives The development of an effective screening method for pancreatic ductal adenocarcinoma (PDAC) is of paramount importance. This study assessed the diagnostic utility in pancreatic diseases of duodenal markers during upper gastrointestinal endoscopy (GIE) or endoscopic ultrasonography. Methods This study prospectively enrolled 299 consecutive participants, including 94 patients with PDACs, 144 patients with other pancreatic diseases, and 61 normal individuals as control subjects. All subjects underwent upper GIE or endoscopic ultrasonography either at Kyushu University Hospital (Fukuoka, Japan) or the Mayo Clinic (Jacksonville, Fla) from October 2011 to July 2014. Duodenal fluid (DF) was collected without secretin stimulation and of carcinoembryonic antigen and S100 calcium-binding protein P (S100P) concentrations were measured. Results Concentrations of S100P in DF were significantly higher in patients with PDAC and chronic pancreatitis than in control subjects (P < 0.01). A logistic regression model that included age found that the sensitivity and specificity of S100P concentration in diagnosing stages 0/IA/IB/IIA PDAC were 85% and 77%, respectively, with an area under the receiver operating characteristic curve of 0.82. Carcinoembryonic antigen concentrations in DF of patients with pancreatic disease did not differ significantly from control subjects. Conclusions Analysis of S100P concentration in DF, in combination with routine screening upper GIE, may facilitate the detection of PDAC..
197. Eriko Maehara, Chikage Mitoma, Gaku Tsuji, Takamichi Ito, Uchi Hiroshi, Yoshinao Oda, Masutaka Furue, Breast angiosarcoma without radiation history, putatively associated with subclinical lymphedema
A case report and review of the Japanese literature, Journal of Dermatology, 10.1111/1346-8138.13917, 44, 10, e266-e267, 2017.10.
198. Yoshiaki Fujimoto, Yuichiro Nakashima, Shun Sasaki, Tomoko Jogo, Kosuke Hirose, Keitaro Edahiro, Shotaro Korehisa, Daisuke Taniguchi, Kensuke Kudou, Yu Nakaji, Ryota Nakanishi, Kouji Andou, Hiroshi Saeki, Eiji Oki, Minako Fujiwara, Yoshinao Oda, Yoshihiko Maehara, Chemoradiotherapy for solitary skeletal muscle metastasis from oesophageal cancer
Case report and brief literature review, Anticancer Research, 10.21873/anticanres.12005, 37, 10, 5687-5691, 2017.10, Background: The incidence of skeletal muscle metastasis from oesophageal cancer is very low, and the treatment strategy has not been established. Case Report: A 77-year-old man underwent oesophagectomy following neoadjuvant chemotherapy for oesophageal squamous cell carcinoma (CT-pT3 N0 M0, CT-pStage II). Fourteen months after surgery, he became aware of a subcutaneous tumour in his left forearm. Computed tomography and fluorodeoxyglucose positron-emission tomography revealed a 65×75 mm intramuscular nodular lesion with a standardized uptake value of 8.5. Further examination by biopsy strongly suggested this was a solitary metastasis from oesophageal cancer. The patient received chemoradiotherapy with two cycles of 5- fluorouracil combined with cisplatin and radiation. Clinical complete response was confirmed by imaging 7 months after chemoradiation and no recurrence has occurred at 20 months since chemoradiation. Conclusion: Radiotherapy or chemoradiotherapy can be an alternative locoregional therapy to surgery for solitary skeletal muscle metastasis..
199. Yukihiko Okumura, Kenichi Kouhashi, Huanlin Wang, Masaki Kato, Yoshihiko Maehara, Yoshihiro Ogawa, Yoshinao Oda, Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma with aggressive biological behavior (adverse clinical course)
A case report, Pathology Research and Practice, 10.1016/j.prp.2017.06.001, 213, 10, 1322-1326, 2017.10, Combined primary hepatic neuroendocrine carcinoma (PHNEC) and hepatocellular carcinoma (HCC) is a very rare malignant hepatic tumor. Its prognosis and histological features are uncertain. Here we report the case of such a tumor in a 70-year-old male Japanese patient with adverse prognosis. The patient underwent a right hepatic lobectomy for a tumor mass that measured 11 × 10 cm in diameter located in the right lobe of the liver, treated with transcatheter arterial chemoembolization (TACE) and percutaneous transhepatic portal vein embolization (PTPE) therapy five weeks before the operation. Histologically, the hepatic tumor was composed of predominantly HCC and admixed with a small part of neuroendocrine carcinoma (NEC). The NEC component was distributed as a collision-type tumor separated by fibrous bands from HCC and the combined-type tumor, focally intermingling with HCC. One month after the surgery, metastasis to abdominal lymph nodes and the lumbar vertebra was detected. Although the additional treatments of systematic chemotherapy and radiation therapy were performed, the patient died 3 months after the initial surgery..
200. Yuki Ikematsu, Yasuto Yoneshima, Kayo Ijichi, Kentaro Tanaka, Taishi Harada, Yoshinao Oda, Yoichi Nakanishi, Isamu Okamoto, Marked response to pembrolizumab in a patient with pulmonary pleomorphic carcinoma highly positive for PD-L1, Lung Cancer, 10.1016/j.lungcan.2017.07.020, 112, 230-231, 2017.10.
201. Naoki Haratake, Gouji Toyokawa, Tetsuzo Tagawa, Yuka Kozuma, Taichi Matsubara, Shinkichi Takamori, Takaki Akamine, Yuichi Yamada, Yoshinao Oda, Yoshihiko Maehara, Positive conversion of PD-L1 expression after treatments with chemotherapy and nivolumab, Anticancer Research, 10.21873/anticanres.12009, 37, 10, 5713-5717, 2017.10, Background/Aim: Few studies have so far described the conversion of programmed death-ligand 1 (PD-L1) after treatment. In particular, the effect of nivolumab on the PD-L1 expression has never been reported. We investigated the changes in PD-L1 expression after chemotherapy and nivolumab treatment and herein describe the detailed clinical course. Patients and Methods: We retrospectively examined the PD-L1 expression in resected specimens and in the re-biopsy specimens of patients with non-small cell lung cancer by immunohistochemical analysis. Results: Four patients underwent a re-biopsy after treatment. Of those, three showed positive conversion of the PD-L1 expression. One patient underwent a re-biopsy after chemotherapy and nivolumab treatment, and the other two cases underwent a re-biopsy after chemotherapy, radiotherapy and nivolumab treatment. Conclusion: These cases suggest the positive conversion of PD-L1 expression after treatments including nivolumab, suggesting that PD-L1 expression must be assessed in not only the resected specimens, but also in the re-biopsied ones..
202. Kazuki Takada, Gouji Toyokawa, Tatsuro Okamoto, Mototsugu Shimokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara, A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non–Small-Cell Lung Cancer Patients, Clinical Lung Cancer, 10.1016/j.cllc.2017.02.004, 18, 5, 572-582.e1, 2017.09, We examined programmed cell death ligand-1 (PD-L1) expression in 499 surgically resected nonsmall-cell lung cancer (NSCLC) patients using the clone SP142 and 4 different cutoff values. PD-L1 expression in NSCLC was shown to vary greatly according to different cutoff values, and to be associated with poor survival in NSCLC patients. This study might be a useful reference to understand the results of the POPLAR and OAK studies. Background Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with antiPD-1 therapy currently the standard treatment for nonsmall-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC. Patients and Methods We examined PD-L1 expression in NSCLC using the clone SP142 of POPLAR and OAK studies. PD-L1 expression in 499 surgically resected NSCLC patients was evaluated using immunohistochemistry using SP142. We set cutoff values as 1%, 5%, 10%, and 50%. Results The samples from 189 (37.9%), 119 (23.8%), 71 (14.2%), and 39 (7.8%) patients were positive for PD-L1 expression at cutoff values of 1%, 5%, 10%, and 50%, respectively. Fisher exact tests showed that PD-L1 positivity was significantly associated with male sex, smoking, advanced stage, the presence of vascular invasion, squamous cell carcinoma, and wild type epidermal growth factor receptor gene mutation status at all cutoff values. Univariate and multivariate survival analyses revealed that PDL1-positive patients had a worse prognosis than PDL1-negative patients only at the 1% cutoff value. Forest plot analyses showed that the 1% cutoff provided a more sensitive value for the prediction of postoperative prognosis. Conclusion PD-L1 expression varied greatly according to different cutoff values. This study might be a useful reference to understand the results of POPLAR and OAK studies and to select patients likely to benefit from atezolizumab..
203. Yuka Hiraki-Hotokebuchi, Yuichi Yamada, Kenichi Kouhashi, Hidetaka Yamamoto, Makoto Endo, Nokitaka Setsu, Kuma Yuki, Takamichi Ito, Yukihide Iwamoto, Masutaka Furue, Yoshinao Oda, Alteration of PDGFRβ-Akt-mTOR pathway signaling in fibrosarcomatous transformation of dermatofibrosarcoma protuberans, Human Pathology, 10.1016/j.humpath.2017.07.001, 67, 60-68, 2017.09, Dermatofibrosarcoma protuberans (DFSP) is a cutaneous mesenchymal tumor of intermediate malignancy and fibroblastic/myofibroblastic differentiation. Fibrosarcomatous (FS) component is a high-grade component of DFSP. The detailed oncogenic difference between DFSP and FS components is not clear. We thus investigated the Akt-mTOR pathway in both components. We used 65 tumor samples obtained from 65 patients. The phosphorylation of Akt-mTOR pathway proteins (Akt, mTOR, 4EBP1, and S6RP) and PDGFRα/β was assessed by immunohistochemical staining, the results of which were confirmed by Western blotting. The immunohistochemical results were as follows: in ordinary DFSP components, p-PDGFRα–positive tumors were 41.9% (18/43 cases), p-PDGFRβ 55.8% (24/43 cases), p-Akt 51.2% (22/43 cases), p-mTOR 39.5% (17/43 cases), p-4EBP1 46.5% (20/43 cases), and p-S6RP 41.8% (18/43 cases); in DFSP components of FS-DFSP, 52.6% (10/19 cases), 47.4% (9/19 cases), 52.6% (10/19 cases), 36.8% (7/19 cases), 52.6% (10/19 cases), and 52.6% (10/19 cases); and in FS components, 45.5% (10/22 cases), 36.4% (8/22 cases), 72.7% (16/22 cases), 54.5% (12/22 cases), 72.7% (16/22 cases), and 68.2% (15/22 cases), respectively. There were significant positive correlations of the phosphorylation of most of the Akt-mTOR pathway proteins (p-Akt, p-mTOR, p-4EBP1, and p-S6RP) with each other (P <.05). Phospho-PDGFRβ was well correlated with the phosphorylation of Akt-mTOR pathway proteins in DFSP components of ordinary and FS-DFSPs, but these correlations were weaker in FS components. This study suggested the association of activation of Akt-mTOR pathway proteins and PDGFR with the progression of DFSP to FS. The Akt-mTOR pathway is thus a potential therapeutic target in imatinib-resistant DFSP/FS..
204. Gouji Toyokawa, Kazuki Takada, Tatsuro Okamoto, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara, High Frequency of Programmed Death-ligand 1 Expression in Emphysematous Bullae-associated Lung Adenocarcinomas, Clinical Lung Cancer, 10.1016/j.cllc.2016.11.011, 18, 5, 504-511.e1, 2017.09, Our objective is to clarify the prevalence of programmed death-ligand-1 (PD-L1) expression in emphysematous bullae (EB)-associated lung adenocarcinomas. Seventy patients (19.0%) were positive for PD-L1 expression. Thirty-six (44.4%) and 29 (58.0%) of 81 and 50 patients with EB and cancer adjoining EB, respectively, were positive for PD-L1 expression. EB-associated lung adenocarcinomas express PD-L1 protein more frequently than those without EB. Objective Emphysematous bullae (EB) are known to be associated with a high incidence of lung cancer; however, the reason for this has yet to be elucidated. The objective of the present study was to clarify the prevalence of programmed death-ligand-1 (PD-L1) expression in EB-associated lung adenocarcinomas. Patients and Methods A total of 369 patients with resected lung adenocarcinoma whose preoperative computed tomography findings were available for the examination of EB were analyzed for PD-L1 expression by immunohistochemistry and evaluated to determine the association between PD-L1 expression and EB-related adenocarcinomas. Results Among 369 patients, EB and cancer adjoining EB (Ca-ADJ) were identified in 81 (22.0%) and 50 (13.6%) patients, respectively. EB and Ca-ADJ were significantly associated with male gender, a smoking habit, a decreased forced expiratory volume in 1 second, a relatively higher tumor grade, advanced T status and stage, the presence of pleural and vessel invasion, invasive pathologic subtypes, and wild-type epidermal growth factor receptor. Seventy patients (19.0%) were positive for PD-L1 expression, whereas the remaining 299 patients (81.0%) were negative. Thirty-six (44.4%) and 29 (58.0%) of 81 and 50 patients with EB and Ca-ADJ, respectively, were positive for PD-L1 expression, which was shown to be significant by the Fisher exact test (P < .001 and P < .001, respectively). Among the 81 lung adenocarcinomas with EB, Ca-ADJ was significantly associated with PD-L1 expression (P = .021). In a multivariate analysis, the presence of Ca-ADJ was found to be an independent predictor of PD-L1 expression. Conclusions EB-associated lung adenocarcinomas express PD-L1 protein more frequently than those without EB..
205. Takaki Akamine, Gouji Toyokawa, Kenichi Kouhashi, Taichi Matsubara, Yuka Kozuma, Naoki Haratake, Shinkichi Takamori, Masakazu Katsura, Kazuki Takada, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara, Highlighted version successful resection of a tracheal metastasis of rectal cancer
A case report, Journal of Thoracic Disease, 10.21037/jtd.2017.07.94, 9, 9, E797-E800, 2017.09, A tracheal metastasis (TM) from non-pulmonary malignancy is extremely rare, and there are very few reports regarding TM. Here, we report a case of the successful tracheal resection of TM of colorectal cancer. A 36-year-old man underwent a surgical resection for the rectal cancer. Approximately 5 years after the surgical resection of the primary rectal cancer, an isolated TM was identified. The patient was successfully treated with a tracheal resection. In conclusion, the current case suggested that the best treatment of the isolated TM might be a surgical resection..
206. Kunio Iura, Kenichi Kouhashi, Takeaki Ishii, Akira Maekawa, Hirofumi Bekki, Hiroshi Otsuka, Yuichi Yamada, Hidetaka Yamamoto, Yoshihiro Matsumoto, Yukihide Iwamoto, Yoshinao Oda, MAGEA4 expression in bone and soft tissue tumors
its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1, Virchows Archiv, 10.1007/s00428-017-2206-z, 471, 3, 383-392, 2017.09, Cancer-testis (CT) antigens have promise as targets for immunotherapy, because of their restricted expression in tumor or testis tissue. MAGEA4 is both a MAGE family member and a CT antigen, and has attracted attention as a potential immunotherapeutic target. We investigated MAGEA4 expression by immunohistochemistry in bone and soft tissue tumor specimens that consisted of 35 malignant or intermediate and 24 benign histological subtypes, in order to evaluate its possible utility as an immunotherapy target and its potential use as a diagnostic marker when combined with another CT antigen, NY-ESO-1. Among these tumors, MAGEA4 was detected in 82.2% of synovial sarcomas, 67.7% of myxoid liposarcomas, 43.8% of osteosarcomas, 41.4% of angiosarcomas, 24.6% of malignant peripheral nerve sheath tumors (MPNSTs), and 21.4% of chondrosarcomas. NY-ESO-1 expression was found in 88.2% of myxoid liposarcomas, 61.1% of synovial sarcomas, 31.3% of osteosarcomas, 21.4% of pleomorphic liposarcomas, 16.7% of desmoplastic small round cell tumors, and 14.3% of chondrosarcomas. Benign tumors and non-tumorous tissue, except for testis tissue, did not express MAGEA4 or NY-ESO-1. Combined use of MAGEA4 and NY-ESO-1 increased the sensitivity, specificity, positive predictive values, and negative predictive values for distinguishing synovial sarcoma from spindle cell tumors and other mimicking tumors, compared to individual use of MAGEA4 or NY-ESO-1. Our results support the immunotherapy targeting MAGEA4 or NY-ESO-1 can be an ancillary therapy in the above-mentioned tumors, and the potential utility of MAGEA4 as an ancillary diagnostic marker for synovial sarcoma combined with NY-ESO-1..
207. Yoshinao Oda, Hidetaka Yamamoto, Kenichi Kouhashi, Yuichi Yamada, Kunio Iura, Takeaki Ishii, Akira Maekawa, Hirofumi Bekki, Soft tissue sarcomas
From a morphological to a molecular biological approach, Pathology International, 10.1111/pin.12565, 67, 9, 435-446, 2017.09, Recently developed molecular genetic techniques have led to the elucidation of tumor-specific genomic alterations and thereby the reclassification of tumor entities of soft tissue sarcoma. A solitary fibrous tumor-mimicking tumor with the AHRR-NCOA2 gene has been isolated as angiofibroma of soft tissue. As for small round cell sarcomas, novel fusion genes such as CIC-DUX4 and BCOR-CCNB3 have been identified in these tumor groups. SMARCB1/INI1 deficient tumors with round cell morphology are also expected to be reclassified in three types, based on the combination of their morphology and genotype. The identification of the MDM2 gene amplification in pleomorphic sarcomas has extended the entity of dedifferentiated liposarcoma (DDLS). Our recent molecular investigations elucidated candidates for novel therapeutic strategies. Activation of the Akt-mTOR pathway was correlated with poor prognosis or tumor grade in spindle cell sarcomas including malignant peripheral nerve sheath tumor. In vitro and in vivo studies of transcription factor Forkhead Box M1 (FOXM1) demonstrated the close correlation between aggressive biological behavior or chemosensitivity and FOXM1 expression in synovial sarcoma, so far. Finally, in regard to the investigation of cancer-testis antigens, myxoid/round cell liposarcoma and synovial sarcoma showed frequent and high expression of PRAME and NY-ESO-1..
208. Ohtsuka Takao, Yasuhisa Mori, Kosei Ishigami, Takaaki Fujimoto, Yoshihiro Miyasaka, Kohei Nakata, Kenoki Ouchida, Eishi Nagai, Yoshinao Oda, Shuji Shimizu, Masafumi Nakamura, Clinical significance of circumportal pancreas, a rare congenital anomaly, in pancreatectomy, American Journal of Surgery, 10.1016/j.amjsurg.2016.11.018, 214, 2, 267-272, 2017.08, Background Circumportal pancreas is a rare congenital pancreatic anomaly. The aim of this study was to clarify the clinical characteristics of patients with circumportal pancreases undergoing pancreatectomy. Methods The medical records of 508 patients who underwent pancreatectomy were retrospectively reviewed. The prevalence of circumportal pancreas and related anatomical variations were assessed. Surgical procedures and postoperative outcomes were compared in patients with and without circumportal pancreas. Results Circumportal pancreas was observed in 9 of the 508 patients (1.7%). In all nine patients, the portal vein was completely encircled by the pancreatic parenchyma above the level of the splenoportal junction, and the main pancreatic duct ran dorsal to the portal vein. The rate of variant hepatic artery did not differ significantly in patients with and without circumportal pancreas. Pancreatic fistula developed more frequently in patients with than without circumportal pancreas (44% vs. 14%, p = 0.03), but other clinical parameters did not differ significantly in these two groups. Conclusions Despite being rare, circumportal pancreas may increase the risk of postoperative pancreatic fistula in patients undergoing pancreatectomy. However, a prospective, large-cohort study is necessary to determine the real incidence of relevant anatomical variations and the definitive clinical significance of this rare anomaly..
209. Shinkichi Takamori, Gouji Toyokawa, Isamu Okamoto, Kazuki Takada, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Masakazu Katsura, Nobutaka Mukae, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Toru Iwaki, Koji Iihara, Yoichi Nakanishi, Yoshihiko Maehara, Discrepancy in programmed cell death-ligand 1 between primary and metastatic non-small cell lung cancer, Anticancer Research, 10.21873/anticanres.11813, 37, 8, 4223-4228, 2017.08, Aim: To investigate the discordance in the programmed cell death-ligand 1 (PD-L1) expression between primary and metastatic tumors and analyze the association between the discordance and the clinical factors in non-small cell lung cancer (NSCLC) patients. Patients and Methods: Twenty-one NSCLC patients who underwent surgery or biopsy for paired primary and metastatic lesions at our Institution from 2005 to 2016 were analyzed. Lesions with the PD-L1 expression being 5% were considered PD-L1-positive. Results: The metastatic sites included the brain (n=16), adrenal gland (n=3), spleen (n=1) and jejunum (n=1). Negative conversion of the primary PD-L1-positive NSCLC and positive conversion of the primary PD-L1-negative NSCLC were observed in 3 (14%) and 2 (10%) cases, respectively. Radiotherapy for the metastatic brain lesion before its resection showed a significant relationship with the positive conversion of the primary PD-L1-negative NSCLC (p=0.048). Conclusion: Radiotherapy-derived effects may contribute to the positive conversion of the primary PD-L1-negative NSCLC..
210. Mio Tanaka, Kenichi Kouhashi, Kei Kushitani, Misa Yoshida, Sho Kurihara, Masumi Kawashima, Yuka Ueda, Ryota Sozaki, Yoshiaki Kinoshita, Yoshinao Oda, Yukio Takeshima, Eiso Hiyama, Tomoaki Taguchi, Yukichi Tanaka, Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M-ALK gene
report of 2 infantile cases and review of the differential diagnosis of infantile pulmonary lesions, Human Pathology, 10.1016/j.humpath.2017.06.013, 66, 177-182, 2017.08, We report 2 infantile cases of pulmonary tumor carrying a chimeric A2M-ALK gene. A2M-ALK is a newly identified anaplastic lymphoma kinase (ALK)–related chimeric gene from a tumor diagnosed as fetal lung interstitial tumor (FLIT). FLIT is a recently recognized infantile pulmonary lesion defined as a mass-like lesion that morphologically resembles the fetal lung. Grossly, FLIT characteristically appears as a well-circumscribed spongy mass, whereas the tumors in these patients were solid and firm. Histologically, the tumors showed intrapulmonary lesions composed of densely proliferating polygonal or spindle-shaped mesenchymal cells with diffuse and dense infiltrations of inflammatory cells forming microcystic or micropapillary structures lined by thyroid transcription factor 1–positive pneumocytes, favoring inflammatory myofibroblastic tumor rather than FLIT. The proliferating cells were immunoreactive for ALK, and A2M-ALK was identified in both tumors with reverse-transcription polymerase chain reaction. The dense infiltration of inflammatory cells, immunoreactivity for ALK, and identification of an ALK-related chimeric gene suggested a diagnosis of inflammatory myofibroblastic tumor. Histologically, most reported FLITs show sparse inflammatory infiltrates and a relatively low density of interstitial cells in the septa, although prominent infiltration of inflammatory cells and high cellularity of interstitial cells are seen in some FLITs. The present cases suggest that ALK rearrangements, including the chimeric A2M-ALK gene, may be present in these infantile pulmonary lesions, especially those with inflammatory cell infiltration. We propose that these infantile pulmonary lesions containing a chimeric A2M-ALK gene be categorized as a specific type of inflammatory myofibroblastic tumor that develops exclusively in neonates and infants..
211. Yuka Hiraki-Hotokebuchi, Yuichi Yamada, Kenichi Kohashi, Hidetaka Yamamoto, Makoto Endo, Nokitaka Setsu, Kuma Yuki, Takamichi Ito, Yukihide Iwamoto, Masutaka Furue, Yoshinao Oda, Alteration of PDGFRβ-Akt-mTOR Pathway Signaling in Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans, Human Pathology, 10.1016/j.humpath.2017.07.001, 2017.07, Dermatofibrosarcoma protuberans (DFSP) is a cutaneous mesenchymal tumor of intermediate malignancy and fibroblastic/myofibroblastic differentiation. Fibrosarcomatous (FS) component is a high-grade component of DFSP. The detailed oncogenic difference between DFSP and FS components is not clear. We thus investigated the Akt-mTOR pathway in both components. We used 65 tumor samples obtained from 65 patients. The phosphorylation of Akt-mTOR pathway proteins (Akt, mTOR, 4EBP1, and S6RP) and PDGFRα/β was assessed by immunohistochemical staining, the results of which were confirmed by western blotting. The immunohistochemical results were as follows: in ordinary DFSP components, p-PDGFRα-positive tumors were 41.9% (18/43 cases), p-PDGFRβ 55.8% (24/43 cases), p-Akt 51.2% (22/43 cases), p-mTOR 39.5% (17/43 cases), p-4EBP1 46.5% (20/43 cases), and p-S6RP 41.8% (18/43 cases); in DFSP components of FS-DFSP, 52.6% (10/19 cases), 47.4% (9/19 cases), 52.6% (10/19 cases), 36.8% (7/19 cases), 52.6% (10/19 cases), and 52.6% (10/19 cases); and in FS components, 45.5% (10/22 cases), 36.4% (8/22 cases), 72.7% (16/22 cases), 54.5% (12/22 cases), 72.7% (16/22 cases), and 68.2% (15/22 cases), respectively. There were significant positive correlations of the phosphorylation of most of the Akt-mTOR pathway proteins (p-Akt, p-mTOR, p-4EBP1, and p-S6RP) with each other (p values <.05). Phospho-PDGFRβ was well correlated with the phosphorylation of Akt-mTOR pathway proteins in DFSP components of ordinary and FS-DFSPs, but these correlations were weaker in FS components. This study suggested the association of activation of Akt-mTOR pathway proteins and PDGFR with the progression of DFSP to FS. The Akt-mTOR pathway is thus a potential therapeutic target in imatinib-resistant DFSP/FS..
212. Takatoshi Fujishita, Tatsuro Okamoto, Takaki Akamine, Shinkichi Takamori, Kazuki Takada, Masakazu Katsura, Gouji Toyokawa, Fumihiro Shoji, Mototsugu Shimokawa, Yoshinao Oda, Yusaku Nakabeppu, Yoshihiko Maehara, Association of MTH1 expression with the tumor malignant potential and poor prognosis in patients with resected lung cancer, Lung Cancer, 10.1016/j.lungcan.2017.04.012, 109, 52-57, 2017.07, Objectives The oxidized purine nucleoside triphosphatase, mutT homolog 1 (MTH1), physiologically sanitizes 8-oxo-dGTP in the nucleotide pool. Previous studies indicated that MTH1 is associated with tumor proliferation and invasion in non-small cell lung cancer (NSCLC) cell lines; however, the role of MTH1 in patients with NSCLC remains unclear. Materials and Methods Two patient cohorts that underwent surgery for NSCLC in our institution were investigated retrospectively. In one cohort consisting of 197 patients, the associations between MTH1 expression and clinicopathological factors or prognosis were analyzed. In another cohort consisting of 41 patients, the relationship between MTH1 expression in the tumors and serum oxidative stress levels (evaluated by the diacron-reactive oxygen metabolites [d-ROMs] test) or antioxidant capacity in the patients (evaluated by the biological antioxidant potential (BAP) test) was analyzed. A total of 238 patients were assessed for MTH1 protein levels using immunohistochemistry. Results Among the 197 patients in the former cohort, 111 (56.3%) exhibited high MTH1 expression, while 86 (43.7%) exhibited low MTH1 expression. Male sex, smoking habit of ≥20 pack-years, squamous cell carcinoma, pathological stage ≥ II, tumor diameter ≥30 mm, lymph node metastases, pleural invasion, lymphatic permeation and vascular infiltration were significantly associated with high MTH1 expression (p < 0.05). The high MTH1 expression group had a significantly worse prognosis than that of the low MTH1 expression group (5-year overall survival: 81.6% vs. 92.3%, p = 0.0011; 5-year disease-free survival: 55.0% vs. 83.7%, p = 0.0002). d-ROMs and BAP test values were significantly higher in the high than in the low MTH1 expression group (p < 0.05). Conclusion This study showed that MTH1 protein expression was closely related to factors associated with a high malignant potential and poor patient survival. MTH1 may be a novel therapeutic target for NSCLC..
213. Kazuki Takada, Tatsuro Okamoto, Masaki Tominaga, Koji Teraishi, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Gouji Toyokawa, Fumihiro Shoji, Masaki Okamoto, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara, Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma
Possible association with PD-L1 expression, PLoS One, 10.1371/journal.pone.0181598, 12, 7, 2017.07, Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells. In the examination of 417 surgically resected primary lung adenocarcinomas, Fisher’s exact tests showed significant associations between high IL-38 expression and high tumor grades, an advanced T status, advanced N status, advanced stage, and the presence of pleural and vessel invasions. Survival analyses by the Kaplan-Meier method showed that patients with high expression of IL-38 had significantly shorter disease-free survival and shorter overall survival after surgery than patients with low expression of IL-38 (log-rank test: P = 0.0021 and P = 0.0035, respectively). Moreover, programmed cell death-ligand 1 (PD-L1)-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: P < 0.0001). In conclusion, IL-38 was expressed in tumor cells of various cancers, and IL-38 expression was associated with poor survival of lung adenocarcinoma patients. IL-38 may affect host immunity or the tumor microenvironment, and contribute to the progression of lung adenocarcinoma..
214. Yuichi Yamada, Izumi Kinoshita, Kenichi Kouhashi, Hidetaka Yamamoto, Yuki Kuma, Takamichi Ito, Kenji Koda, Atsushi Kisanuki, Manabu Kurosawa, Michiko Yoshimura, Masutaka Furue, Yoshinao Oda, HIF-1α, MDM2, CDK4, and p16 expression in ischemic fasciitis, focusing on its ischemic condition, Virchows Archiv, 10.1007/s00428-017-2122-2, 471, 1, 117-122, 2017.07, Ischemic fasciitis is a benign myofibroblastic lesion, occurring in the sacral region or proximal thigh of elderly or bedridden individuals. The pathogenesis of ischemic fasciitis is thought to be based on ischemic condition; however, it has never been demonstrated. In this study, we examined the expression of ischemia-associated proteins in ischemic fasciitis by immunohistochemical and genetic methods. Specifically, this study aimed to reveal the expression of HIF-1α, MDM2, CDK4, p16, and gene amplification of MDM2 gene. Seven cases of ischemic fasciitis from among the soft-tissue tumors registered at our institution were retrieved. Histopathological findings were as follows: poorly demarcated nodular masses, a proliferation of spindle-shaped fibroblastic or myofibroblastic cells with oval nuclei and eosinophilic or pale cytoplasm, zonal fibrinous deposition, pseudocystic degeneration, granulation-like proliferation of capillary vessels, ganglion-like cells, myxoid or hyalinized stroma, and chronic inflammatory infiltration. Immunohistochemically, the spindle cells were positive for HIF-1α (7/7 cases), MDM2 (4/7 cases), CDK4 (4/7 cases), p16 (7/7 cases), p53 (2/7 case), cyclin D1 (7/7 cases), and alpha-smooth muscle actin (6/7 cases). Neither MDM2 gene amplification nor USP6 gene split signal was detected in any case. Overexpression of the above proteins may be associated with the pathogenic mechanism of ischemic fasciitis. It is noted that the immunohistochemical positivity of MDM2, CDK4, and p16 do not necessarily indicate malignant neoplasm such as dedifferentiated liposarcoma..
215. Tetsuyuki Miyazaki, Yoshihiro Ohishi, Yoshihiro Miyasaka, Yasunori Oda, Shinichi Aishima, Keigo Ozono, Atsushi Abe, Eishi Nagai, Masafumi Nakamura, Yoshinao Oda, Molecular Characteristics of Pancreatic Ductal Adenocarcinomas with High-Grade Pancreatic Intraepithelial Neoplasia (PanIN) Are Different from Those without High-Grade PanIN, Pathobiology, 10.1159/000455194, 84, 4, 192-201, 2017.07, We reported that pancreatic ductal adenocarcinomas (PDACs) without high-grade pancreatic intraepithelial neoplasia (PanIN) in the vicinity had worse prognoses than PDACs with high-grade PanIN. However, the molecular characteristics of PDACs with and without high-grade PanIN have not been compared. The aim of this study is to clarify the molecular characteristics of PDACs with and without high-grade PanIN. Method and Results: We reviewed all of a consecutive series of 100 patients with PDACs and divided them into 2 groups: The PDACs with PanIN-2 or PanIN-3 in the background (the PanIN-high group, n = 60) and the PDACs without PanIN-2 or PanIN-3 in the background (the PanIN-low group, n = 40). We evaluated the p53, p16, and SMAD4 expressions in the invasive ductal carcinoma (IDC) components by immunohistochemical staining. KRAS mutation was also analyzed in 80 tumors. The PanIN-low group showed significantly more frequent "high p53 expression" and "loss of SMAD4 expression" than the PanIN-high group (p = 0.048 and p = 0.019, respectively). Loss of p16 expression was not significantly different between the groups. The rate of KRAS wild type was significantly higher in the PanIN-low group than the PanIN-high group (p = 0.024). Conclusions: Our results demonstrated that the molecular characteristics in the PDACs with high-grade PanIN were different from those in the PDACs without high-grade PanIN. PDACs without high-grade PanIN may develop via a pathway other than the PanIN-carcinoma sequence..
216. Yasunori Oda, Shinichi Aishima, Koji Shindo, Minoru Fujino, Yusuke Mizuuchi, Masami Hattori, Tetsuyuki Miyazaki, Masao Tanaka, Yoshinao Oda, SLC2A1/GLUT1 expression in mural nodules of intraductal papillary mucinous neoplasm of the pancreas, Human Pathology, 10.1016/j.humpath.2017.03.008, 65, 71-78, 2017.07, In intraductal papillary mucinous neoplasms (IPMNs), the presence of a mural nodule showing a papillary or nodular proliferation of tumor cells in the dilated pancreatic duct is an indication for resection of IPMN. Solute carrier family 2, facilitated glucose transporter member 1, known as glucose transporter type 1 (SLC2A1/GLUT1) mediates cellular glucose uptake in many carcinomas and is correlated with increased 18F-fluorodeoxyglucose (18F-FDG) uptake. We examined SLC2A1/GLUT1 expression in the mural nodules of 180 IPMN specimens to distinguish malignant/benign tumors. A mural nodule was detected in 80 (44.4%) of the IPMNs, and was detected in 18.6% (13/70) of the IPMN-low (dysplasia) specimens, 36.1% (13/36) of the IPMN-int, 93.3% (28/30) of the IPMN-high, and 59.1% (26/44) of the IPMN-inv (with an associated invasive carcinoma) specimens. The sensitivity for detecting mural nodules was 81.7% by endoscopic ultrasonography, 70% by contrast-enhanced computed tomography and 54% by endoscopic retrograde cholangiopancreatography. SLC2A1/GLUT1 expression in the mural nodules was recognized in the basal and basolateral cytomembrane of tumor cells and was expressed in 15.4% (2/13) of the IPMN-low, 15.4% (2/13) of the IPMN-int, 71.4% (20/28) of the IPMN-high and 84.6% (22/26) of the IPMN-inv groups. The SLC2A1/GLUT1 expression was significantly higher in the IPMN-high and IPMN-inv mural nodules than in those of the IPMN-low and IPMN-int groups. Our findings suggest that SLC2A1/GLUT1 is expressed late in the adenoma-carcinoma sequence during carcinogenesis in IPMN, and SLC2A1/GLUT1 act as therapeutic target for malignant IPMN..
217. Daisuke Imai, Tomoharu Yoshizumi, Shinji Okano, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, shinji itoh, Yuji Soejima, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara, The prognostic impact of programmed cell death ligand 1 and human leukocyte antigen class I in pancreatic cancer, Cancer Medicine, 10.1002/cam4.1087, 6, 7, 1614-1626, 2017.07, Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive tumor-microenvironment (TME) that supports the growth of tumors and mediates tumors enabling evasion of the immune system. Expression of programmed cell death ligand 1 (PD-L1) and loss of human leukocyte antigen (HLA) class I on tumor cells are methods by which tumors escape immunosurveillance. We examined immune cell infiltration, the expression of PD-L1 and HLA class I by PDA cells, and the correlation between these immunological factors and clinical prognosis. PDA samples from 36 patients were analyzed for HLA class I, HLA-DR, PD-L1, PD-1, CD4, CD8, CD56, CD68, and FoxP3 expression by immunohistochemistry. The correlations between the expression of HLA class I, HLA-DR, PD-L1 or PD-1 and the pattern of tumor infiltrating immune cells or the patients’ prognosis were assessed. PD-L1 expression correlated with tumor infiltration by CD68+ and FoxP3+ cells. Low HLA class I expression was an only risk factor for poor survival. PD-L1 negative and HLA class I high-expressing PDA was significantly associated with higher numbers of infiltrating CD8+ T cells in the TME, and a better prognosis. Evaluation of both PD-L1 and HLA class I expression by PDA may be a good predictor of prognosis for patients. HLA class I expression by tumor cells should be evaluated when selecting PDA patients who may be eligible for treatment with PD-1/PD-L1 immune checkpoint blockade therapies..
218. Katsumi Takizawa, Kenichi Kouhashi, Takahito Negishi, Kenichi Taguchi, Yuichi Yamada, Motonobu Nakamura, Yoshinao Oda, A exceptional collision tumor of primary adrenal angiosarcoma and non-functioning adrenocortical adenoma, Pathology Research and Practice, 10.1016/j.prp.2017.04.017, 213, 6, 702-705, 2017.06, Primary adrenal angiosarcoma is an extremely rare vascular tumor. We report a case of a 63-year-old man with a collision tumor of epithelioid angiosarcoma and adrenocortical adenoma of the right adrenal gland. The adrenal tumor was incidentally observed by a preoperative computed tomography (CT) scan of penis squamous cell carcinoma. The patient underwent a right laparoscopic adrenalectomy, and the tumor size measured 34 × 34 × 15 mm. Histological examination revealed two different tumor cell proliferations, namely epithelioid angiosarcoma and adrenocortical adenoma. He had no symptoms or abnormality in his endocrine studies, so the adrenocortical adenoma was considered non-functioning. Three months after the adrenalectomy, bilateral pleural metastasis was observed by CT scan and pleural biopsy. Paclitaxel monotherapy was performed, and the tumor retreated. The patient died one and a half years after the adrenalectomy, but the cause of death was believed to be another disease (metastatic penis squamous cell carcinoma). To the best of our knowledge, this is the fourth report of primary adrenal angiosarcoma combined with adrenocortical adenoma..
219. Hirofumi Bekki, Hidetaka Yamamoto, Katsumi Takizawa, Takeshi Iwasaki, Hiroshi Otsuka, Yuichi Yamada, Kenichi Kouhashi, Katsumi Harimaya, Yukihide Iwamoto, Yoshinao Oda, Claudin 6 expression is useful to distinguish myxofibrosarcomas from other myxoid soft tissue tumors, Pathology Research and Practice, 10.1016/j.prp.2016.12.001, 213, 6, 674-679, 2017.06, Myxofibrosarcoma (MFS) is characterized by abundant myxoid stroma, a wide spectrum of cytological atypia, and frequent local recurrence. Some soft tissue tumors with myxoid stroma can histologically mimic MFS, but have different biological behaviors. Here we sought to identify a useful diagnostic marker for MFS. After our analysis of the gene expression dataset from the Gene Expression Omnibus database, we focused on claudin 6 (CLDN 6). The status of CLDN 6 was assessed by immunohistochemistry in 61 samples of MFS and other (benign) myxoid soft tissue tumors (28 myxoma samples, 12 nodular fasciitis samples), 18 low-grade fibromyxoid sarcoma, 30 myxoid liposarcoma, 29 extraskeletal myxoid chondrosarcoma and 27 dedifferentiated liposarcoma with myxoid feature samples. The correlation between the expression of CLDN 6 and clinicopathological findings in MFS was also investigated. Immunohistochemically, high expression of CLDN 6 was observed in approx. 65% of the MFSs, whereas the benign soft tissue tumors did not show a high expression of CLDN 6. The expression of CLDN 6 in the MFS was significantly higher than those of other tumor specimens. Among the MFSs, the high expression of CLDN 6 was correlated with high FNCLCC grades and high AJCC stages. CLDN 6 may be useful for the differential diagnosis from benign myxoid tumor and for predicting the aggressive biological behavior of MFS..
220. Huanlin Wang, Kenichi Kouhashi, Tomoharu Yoshizumi, Yukihiko Okumura, Yuki Tanaka, Masahiro Shimokawa, Takeshi Iwasaki, Shinichi Aishima, Yoshihiko Maehara, Yoshinao Oda, Coexpression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression of PTEN and poor prognosis in patients with hepatocellular carcinoma, Human Pathology, 10.1016/j.humpath.2017.03.007, 64, 69-75, 2017.06, Spalt-like transcriptional factor 4 (SALL4), a stem marker, is reactivated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex, which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study, we investigated the expression status of SALL4, HDAC1, and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the posthepatectomy specimens of 135 patients with hepatocellular carcinoma who were treated at our hospital. Ninety-two frozen samples were subjected to quantitative reverse-transcription polymerase chain reaction analysis to detect the messenger RNA levels of PTEN. Seventy-six (56%) of 135 patients were positive for SALL4, and this group had a higher prevalence of hepatitis B antigen, a higher value of α-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKAII) and poor histologic differentiation. The 5-year survival rate was significantly lower in the SALL4-positive group. High HDAC1 expression (51%) was correlated with a poor histologic differentiation and a poor prognosis. High HDAC2 expression (46%) was associated with a higher prevalence of hepatitis B antigen positivity, a poor histologic differentiation and higher prevalence of vascular invasion, and a lower 5-year survival rate. Coexpression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression of PTEN. Moreover, multivariable analysis revealed that coexpression of SALL4 with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus suggested that the combination of SALL4, HDAC1, and HDAC2 may provide a potential target for molecular therapy..
221. Takeaki Ishii, Kenichi Kouhashi, Hiroshi Ootsuka, Kunio Iura, Akira Maekawa, Yuichi Yamada, Hirofumi Bekki, Masato Yoshimoto, Hidetaka Yamamoto, Yukihide Iwamoto, Yoshinao Oda, Comparison between retroperitoneal leiomyosarcoma and dedifferentiated liposarcoma, Pathology Research and Practice, 10.1016/j.prp.2017.04.022, 213, 6, 634-638, 2017.06, It is important to distinguish between leiomyosarcoma (LMS) and dedifferentiated liposarcoma (DDLS) in the retroperitoneum. The dedifferentiated component of DDLS shows an LMS-like morphology in some cases; thus, detailed evaluation is necessary to achieve an accurate diagnosis. Immunohistochemically, MDM2 and myogenic markers provide clues for the diagnoses. However, immunoreactivity for MDM2 and myogenic markers has not been well studied in retroperitoneal LMS and DDLS. Here, we compared the clinicopathological data of 20 retroperitoneal tumors initially diagnosed as LMS with that of 36 cases of retroperitoneal DDLS and conducted an immunohistochemical study. Four (20%) of the cases initially diagnosed as LMS were immunoreactive for MDM2. Fifteen cases (41.7%) of DDLS showed positive expression of two or more myogenic markers. The patients with LMS with MDM2 overexpression were older than the patients with LMS without MDM2 overexpression (P = 0.0328). LMS with MDM2 overexpression showed a worse prognosis than DDLS (P = 0.0408). No significant difference in prognosis was found between LMS without MDM2 overexpression and DDLS with myogenic differentiation. In conclusion, we recommend that systemic MDM2 expression analysis be performed in cases of retroperitoneal sarcoma. Overdependence on the expression of myogenic markers could lead to misdiagnosis in distinguishing LMS from DDLS..
222. Murasaki Aman, Yoshihiro Ohishi, Hiroko Imamura, Tomoko Shinozaki, Nobuko Yasutake, Kiyoko Kato, Yoshinao Oda, Expression of protease-activated receptor-2 (PAR-2) is related to advanced clinical stage and adverse prognosis in ovarian clear cell carcinoma, Human Pathology, 10.1016/j.humpath.2017.04.008, 64, 156-163, 2017.06, Recent studies demonstrated that protease-activated receptor-2 (PAR-2) correlates with tumor progression in various tissues. On the other hand, oxidative stress arising from endometriosis has been considered a cause of carcinogenesis in ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative stress up-regulates PAR-2 expression, and we conducted the present study to investigate the PAR-2 expression and its relation to clinicopathological factors and oxidative stress in OCCC. We performed an immunohistochemical evaluation in 95 cases of OCCC. For the evaluation of oxidative stress markers, 31 cases of ovarian endometrioid carcinoma (OEC) were also examined. No significant differences in the expression of cyclooxygenase-2 and inducible nitric oxide synthase were observed between OCCC and OEC. Sixty-two percent of the OCCC cases showed high 8-hydroxydeoxyguanosine expression, whereas all of the OEC cases showed almost negative immunoreactivities. The presence of endometriosis did not affect the expression of these oxidative stress markers or prognosis. High PAR-2 expression was observed in 20% (14/71) of the early International Federation of Gynecology and Obstetrics (FIGO) stage cases and 58% (14/24) of the advanced FIGO stage cases. High PAR-2 expression was significantly correlated with advanced FIGO stage and shorter overall survival. We found no correlations between PAR-2 expression and oxidative stress in OCCC. Our results suggest that PAR-2 plays an important role in the progression of OCCC. The expression of 8-hydroxydeoxyguanosine is a characteristic finding of OCCC, indicating that the injury of DNA by oxidative stress may be involved in the carcinogenesis of OCCC..
223. Sho Nishimura, Eiji Oki, Kouji Andou, Makoto Iimori, Yu Nakaji, Yuichiro Nakashima, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara, High ubiquitin-specific protease 44 expression induces DNA aneuploidy and provides independent prognostic information in gastric cancer, Cancer Medicine, 10.1002/cam4.1090, 6, 6, 1453-1464, 2017.06, Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39.6%) than in gastric normal mucosa (mean, 14.6%) (P < 0.0001). DNA aneuploidy was observed in 124 gastric cancer cases and high USP44 expression in cancer strongly correlated with DNA aneuploidy (P = 0.0005). The overall survival was significantly poorer in the high USP44 expression group compared with the low USP44 group (P = 0.033). Notably, USP44 expression had no prognostic impact in the diploid subgroup; however, high USP44 expression was a strong poor prognostic factor for progression-free survival (P = 0.018) and overall survival (P = 0.036) in the aneuploid subgroup. We also confirmed that stable overexpression of USP44 induced somatic copy-number aberrations in hTERT-RPE-1 cells (50.6%) in comparison with controls (6.6%) (P < 0.0001). Collectively, our data show USP44 has clinical impact on the induction of DNA aneuploidy and poor prognosis in the CIN gastric cancer subtype..
224. Koichiro Yoshimaru, Tomoaki Taguchi, Satoshi Obata, Junkichi Takemoto, Yoshiaki Takahashi, Tsuyoshi Iwanaka, Yusuke Yanagi, Masaaki Kuda, kina miyoshi, Toshiharu Matsuura, Yoshiaki Kinoshita, Takako Yoshioka, Atsuko Nakazawa, Yoshinao Oda, Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological diagnosis of congenital and acquired isolated hypoganglionosis, Virchows Archiv, 10.1007/s00428-017-2128-9, 470, 6, 679-685, 2017.06, Isolated hypoganglionosis (IHG) has been proposed as a distinct entity with two subtypes: congenital IHG (CIHG) and acquired IHG (AIHG). However, due to the rarity of the disease and the lack of defining histological criteria, the concept of IHG is not widely accepted. We studied paraffin-embedded intestinal specimens from 79 patients diagnosed with Hirschsprung’s disease (HD) (n = 49), CIHG (n = 25), and AIHG (n = 5) collected between January 1996 and December 2015. Histopathological diagnosis of HD, CIHG, and AIHG was confirmed by hematoxylin and eosin staining and immunohistochemical staining using Hu C/D and CD56. We evaluated (immuno)histopathological findings, counted the number of ganglion cells, and measured the size of Auerbach’s plexus. Hu C/D labeled neuronal cell bodies, whereas CD56 was detected in all neuronal components. In HD, all ganglion cells in Auerbach’s plexus in the normoganglionic segment (NGS) were immunoreactive for Hu C/D, whereas in the aganglionic segment (AGS), these were replaced by CD56-positive extrinsic nerve fibers and bundles. The number of ganglion cells in AIHG and CIHG was significantly lower than in the NGS of HD (p < 0.05). Auerbach’s plexus was significantly smaller in CIHG (p < 0.05) but in AIHG equivalent to the NGS in HD. In summary, immunostaining for Hu C/D and CD56 is useful for definitive histopathological diagnosis of IHG..
225. Kenzo Sonoda, H. Yahata, Okugawa Kaoru, Kaneki Eisuke, K. Nakatsuki, M. Naka, N. Terado, F. Ookubo, Yoshinao Oda, Tsunehisa Kaku, Kiyoko Kato, Isthmic-vaginal cytological findings after a trachelectomy for early-stage cervical cancer, Cytopathology, 10.1111/cyt.12379, 28, 3, 243-245, 2017.06.
226. Toshimitsu Nishijima, Hidetaka Yamamoto, Takafumi Nakano, Yui Hatanaka, Ken ichi Taguchi, Muneyuki Masuda, Yoshinao Oda, Low-grade intraductal carcinoma (low-grade cribriform cystadenocarcinoma) with tumor-associated lymphoid proliferation of parotid gland, Pathology Research and Practice, 10.1016/j.prp.2017.02.019, 213, 6, 706-709, 2017.06, We report a rare case of low-grade intraductal carcinoma with tumor-associated lymphoid proliferation (TALP) in the parotid gland of a 75-year-old woman. Grossly, the tumor was solid and cystic. Histologically, the tumor consisted of a papillary-cystic, micropapillary, or focally cribriform proliferations of epithelial cells with low-grade cytological atypia. The interspaces between the epithelial components were filled with prominent lymphoid stroma and lymphoid follicles, superficially mimicking Warthin tumor. The neoplastic epithelial cells were positive for S100 protein by immunohistochemical staining. There was an attenuated layer of myoepithelial cells all around the epithelial components, indicating a non-invasive (in situ) nature. Although TALP is a rare finding in intraductal carcinoma, it should be considered as a histological variation of this kind of tumor. The relationship between intraductal carcinoma, low-grade cribriform cystadenocarcinoma, low-grade salivary duct carcinoma, and salivary duct carcinoma in situ is also discussed in this report..
227. Yoshiki Asayama, Akihiro Nishie, Kosei Ishigami, yasuhiro ushijima, Yukihisa Takayama, Daisuke Okamoto, nobuhiro fujita, Ohtsuka Takao, Tomoharu Yoshizumi, Shinichi Aishima, Yoshinao Oda, Hiroshi Honda, Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma, European Radiology, 10.1007/s00330-016-4621-y, 27, 6, 2563-2569, 2017.06, Objectives: To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). Methods: This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT − attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT − attenuation value at unenhanced CT)] × 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. Results: The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). Conclusions: The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. Key points: • Dynamic contrast study can evaluate the aggressiveness of extrahepatic cholangiocarcinoma. • A lower washout ratio was an independent prognostic factor for overall survival. • CT can predict survival and inform decisions on surgical options or chemotherapy..
228. Satoshi Tsutsumi, Hiroshi Saeki, Yuichiro Nakashima, Shuhei Ito, Eiji Oki, Masaru Morita, Yoshinao Oda, Shinji Okano, Yoshihiko Maehara, Programmed death-ligand 1 expression at tumor invasive front is associated with epithelial-mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma, Cancer Science, 10.1111/cas.13237, 108, 6, 1119-1127, 2017.06, Programmed death-ligand 1 (PD-L1) plays a crucial role in the host immune system in cancer progression. The gene promoter region of PD-L1 also contains a binding site for ZEB1, a transcription factor related to epithelial-mesenchymal transition (EMT). The purpose of this study was to clarify the relationship between PD-L1 and EMT and its clinical importance in esophageal squamous cell carcinoma (ESCC). PD-L1 and ZEB1 expression at the tumor invasive front was examined by immunohistochemistry in resected specimens from 90 patients with ESCC who underwent surgery without preoperative therapy, and their expression and clinicopathological factors were compared. ZEB1 and PD-L1 expression was determined in TE8 cells, which demonstrate the EMT phenotype, following ZEB1 knockdown by siZEB1. TE5, TE6 and TE11 cells with non-EMT phenotype were also used for studies of TGF-β1-dependent EMT induction and ZEB1 and PD-L1 expression. In cases of high PD-L1 expression at the invasive front, significantly greater depth of tumor invasion, EMT, and less CD8+ lymphocyte infiltration were observed. High PD-L1 expression was also associated with worse overall and relapse-free survival. A correlation was observed between PD-L1 and ZEB1 expression. In TE8 cells, siZEB1 suppressed PD-L1 and promoted E-cadherin mRNA and protein expression. TGF-β1 induced EMT and surface expression of PD-L1 in TE5, TE6 and TE11 cell lines. PD-L1 expression at the ESCC invasive front was related to ZEB1 expression, EMT and poor prognosis. We suggest that a cooperative mechanism bridging between tumor immune avoidance and EMT contributes to tumor malignancy in ESCC..
229. Gouji Toyokawa, Kazuki Takada, Tatsuro Okamoto, Satoshi Kawanami, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Masakazu Katsura, Yuichi Yamada, Fumihiro Shoji, Shingo Baba, Takeshi Kamitani, Yoshinao Oda, Hiroshi Honda, Yoshihiko Maehara, Relevance Between Programmed Death Ligand 1 and Radiologic Invasiveness in Pathologic Stage I Lung Adenocarcinoma, Annals of Thoracic Surgery, 10.1016/j.athoracsur.2016.12.025, 103, 6, 1750-1757, 2017.06, Background Programmed death ligand 1 (PD-L1) was reported to predict the response of immunotherapy; however, the association between PD-L1 expression and radiologic and pathologic features has yet to be elucidated. Methods In all, 292 patients with resected pathologic stage I adenocarcinoma were analyzed for PD-L1 expression by immunohistochemistry and evaluated to determine the association between PD-L1 expression and the radiologic/pathologic invasiveness. Specifically, the radiologic invasiveness and noninvasiveness were determined based on the consolidation/tumor ratio, with a cutoff value of 0.25 by thin-section computed tomography. Results Among 292 patients, 47 (16.1%) were positive for PD-L1 expression; the remaining 245 patients (83.9%) were negative for PD-L1 expression. Fisher's exact test demonstrated that PD-L1 expression was significantly associated with a higher consolidation/tumor ratio (p = 0.029) and higher maximum standardized uptake value (p = 0.004). The mean values of consolidation/tumor ratio and maximum standardized uptake in patients with and without PD-L1 expression were 0.845 ± 0.052 and 7.241 ± 0.795, and 0.607 ± 0.023 and 3.60 ± 0.364, respectively (p < 0.001 and p < 0.001, respectively). Among 47 adenocarcinomas harboring PD-L1 expression, the frequencies of PD-L1 expression for consolidation/tumor ratios of 0, 0.1 to 0.25, 0.26 to 0.5, and 0.51 or more were 6.4%, 2.1%, 4.3%, and 87.2%, respectively (p = 0.007). Pathologically, PD-L1 was identified exclusively only in more invasive subtypes, not in less invasive ones, such as atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant ones (p < 0.001). Conclusions Expression of PD-L1 was significantly associated with radiologic/pathologic invasive adenocarcinomas. This study provides the first evidence of the radiologic and pathologic invasiveness in resected pathologic stage I adenocarcinoma with PD-L1 expression..
230. Sho Endo, Kohei Nakata, Kenoki Ouchida, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Kazuhiro Koikawa, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Yusuke Mizuuchi, Chika Iwamoto, Masaharu Murata, Taiki Moriyama, Yoshihiro Miyasaka, Ohtsuka Takao, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura, Autophagy Is Required for Activation of Pancreatic Stellate Cells, Associated With Pancreatic Cancer Progression and Promotes Growth of Pancreatic Tumors in Mice, Gastroenterology, 10.1053/j.gastro.2017.01.010, 152, 6, 1492-1506.e24, 2017.05, Background & Aims Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor environment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. PSCs have morphologic and functional similarities to hepatic stellate cells, which undergo autophagy to promote fibrosis and tumor growth. We investigated whether autophagy activates PSCs, which promotes development of the tumor stroma and growth of pancreatic tumors in mice. Methods We used immunofluorescence microscopy and immunohistochemistry to analyze pancreatic tumor specimens from 133 patients who underwent pancreatectomy in Japan from 2000 to 2009. PSCs were cultured from pancreatic tumor tissues or tissues of patients with chronic pancreatitis; these were analyzed by immunofluorescence microscopy, immunoblots, quantitative reverse transcription polymerase chain reaction, and in assays for invasiveness, proliferation, and lipid droplets. Autophagy was inhibited in PSCs by administration of chloroquine or transfection with small interfering RNAs. Proteins were knocked down in immortalized PSCs by expression of small hairpin RNAs. Cells were transplanted into pancreatic tails of nude mice, and tumor growth and metastasis were quantified. Results Based on immunohistochemical analyses, autophagy was significantly associated with tumor T category (P =.018), histologic grade (P =.001), lymph node metastases (P <.001), stage (P =.009), perilymphatic invasion (P =.001), and perivascular invasion (P =.003). Autophagy of PSCs was associated with shorter survival times of patients with pancreatic cancer. PSC expression of microtubule-associated protein 1 light chain 3, a marker of autophagosomes, was associated with poor outcomes (shorter survival time, disease recurrence) for patients with pancreatic cancer (relative risk of shorter survival time, 1.56). Immunoblots showed that PSCs from pancreatic tumor samples expressed higher levels of markers of autophagy than PSCs from chronic pancreatitis samples. Inhibitors of autophagy increased the number of lipid droplets of PSCs, indicating a quiescent state of PSCs, and reduced their production of ECM molecules and interleukin 6, as well as their proliferation and invasiveness in culture. PSCs exposed to autophagy inhibitors formed smaller tumors in nude mice (P =.001) and fewer liver metastases (P =.018) with less peritoneal dissemination (P =.018) compared to PSCs not exposed to autophagy inhibitors. Conclusions Autophagic PSCs produce ECM molecules and interleukin 6 and are associated with shorter survival times and disease recurrence in patients with pancreatic cancer. Inhibitors of PSC autophagy might reduce pancreatic tumor invasiveness by altering the tumor stroma..
231. Kenjiro Date, Ohtsuka Takao, Takaaki Fujimoto, Koji Tamura, Hideyo Kimura, Taketo Matsunaga, Naoki Mochidome, Tetsuyuki Miyazaki, Yasuhisa Mori, Yoshinao Oda, Masafumi Nakamura, Masao Tanaka, Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas, Annals of Surgery, 10.1097/SLA.0000000000001755, 265, 5, 969-977, 2017.05, Objective: To clarify clonality of distinct multisegmental main duct (MD)-intraductal papillary mucinous neoplasms (IPMNs) using microarray analysis. Background: IPMNs represent a pancreatic ductal cell field defect, which causes multiple occurrences of lesions. In addtion, it has been speculated that MD-IPMNs display features of monoclonal skip progression. Methods: Total RNA was extracted from fresh-frozen tissue samples of metachronous MD-IPMNs and nonneoplastic pancreas tissue from the same pancreas from two individuals, and whole human genome microarray analysis was performed. Formalin-fixed paraffin-embedded tissue specimens from 28 distinct IPMNs were then collected from 12 patients, genomic DNA was extracted, and GNAS/KRAS mutational status was investigated. Immunohistochemical analysis was performed to validate the expression pattern of the indicated proteins. Results: Microarray analysis revealed that metachronous MD-IPMNs from the same individual displayed pair-wise correlation coefficients of 0.9523 and 0.9512. In contrast, MD-IPMNs of the same histological grade from different individuals displayed coefficients of 0.8092 and 0.8211. Scatter plot analysis revealed that metachronous MD-IPMNs from the same individual displayed a closer linear relationship. Furthermore, heat map and hierarchical cluster analyses revealed that metachronous MD-IPMNs from the same individual were classified in the same branch, and the gene expression patterns were similar. The GNAS/KRAS mutational statuses of distinct MD-IPMNs were consistent with each other. Immunohistochemical assessment of five specific proteins demonstrated that the same expression pattern between two lesions was observed in 95% of the samples. Conclusions: These findings using molecular analyses indicate that MD-IPMNs might display features of monoclonal skip progression..
232. Hirofumi Bekki, Kenichi Kouhashi, Yuichi Yamada, Kunio Iura, Takeaki Ishii, Akira Maekawa, Hiroshi Otsuka, Hidetaka Yamamoto, Michiyuki Hakozaki, Kazuki Nabeshima, Yukihide Iwamoto, Yoshinao Oda, Phosphorylation of STAT3 in undifferentiated pleomorphic sarcoma is correlated with a favorable prognosis, Pathobiology, 10.1159/000448524, 84, 3, 161-169, 2017.05, Objective: The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a role in various biological processes. Phosphorylated STAT3 (p-STAT3) functions as a transcriptional factor, and suppressor of cytokine signaling 3 (SOCS3) is a potential inhibitor of STAT3. Here, we analyzed the status of the JAK-STAT pathway in undifferentiated pleomorphic sarcoma (UPS). Methods: We performed immunohistochemistry in 79 samples of UPS and Western blotting in 10 frozen samples. We also examined alterations in protein expression in the JAK-STAT pathway after the inhibition of phosphorylated Akt (p-Akt) or extracellular signal-regulated kinase (p-Erk) in vitro. Results: Immunohistochemically, p-STAT3 and SOCS3 were positive in 59.7 and 55.8%, respectively. Positivity for p-STAT3 was significantly correlated with a better prognosis (p = 0.0006) and negatively with SOCS3 expression (p = 0.0223). Positivity for SOCS3 was significantly correlated with a worse prognosis (p = 0.0001). Western blotting analysis revealed that p-STAT3 expression was lower in tumor than in normal tissue. In vitro results demonstrated that there was no detectable change in the expression of p-STAT3 regardless of the status of p-Akt or p-Erk. Conclusion: P-STAT3 may be a useful prognostic factor for UPS..
233. Suguru Fukushima, Makoto Endo, Yoshihiro Matsumoto, Jun-Ichi Fukushi, Tomoya Matsunobu, Ken Ichi Kawaguchi, Nokitaka Setsu, Keiichiro Iida, Nobuhiko Yokoyama, Makoto Nakagawa, Kenichiro Yahiro, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima, Potential therapeutic target in malignant peripheral nerve sheath tumor, PLoS One, 10.1371/journal.pone.0178064, 12, 5, 2017.05, Background Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1α in MPNSTs is unclear. Methods The expression of HIF-1α was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1α.specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1α. Results The nuclear expression of HIF-1α was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1α was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P ≤ 0.0001) analyses. HIF-1α knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1α, effectively inhibited the growth of MPNST cells and induced their apoptosis. Conclusion Inhibition of HIF-1α signaling is a potential treatment option for MPNSTs..
234. Kyoko Yamashita, Kenichi Kouhashi, Yuichi Yamada, Yoshihiro Nishida, Hiroshi Urakawa, Yoshinao Oda, Shinya Toyokuni, Primary extraskeletal osteosarcoma
a clinicopathological study of 18 cases focusing on MDM2 amplification status, Human Pathology, 10.1016/j.humpath.2017.02.007, 63, 63-69, 2017.05, Extraskeletal osteosarcoma (ESOS) is an uncommon malignant neoplasm. Most ESOSs are high grade, although some low-grade cases have been reported. A few cases of ESOS with MDM2 amplification have also been reported, suggesting some similarity to skeletal low-grade osteosarcoma such as parosteal osteosarcoma, where MDM2 is often amplified. However, the frequency of low-grade cases and cases with MDM2 amplification among ESOSs remains unknown, and their relationship is unclear. To clarify this, we examined 18 primary ESOS cases clinically, pathologically, and genetically, focusing on their MDM2 amplification status. Our cases comprised 10 men and 8 women whose mean age was 58.6 years; the most common site of the lesion was the thigh and buttock. There were one histologically low-grade case evaluated by biopsy specimen with an aggressive course and 2 relatively low-grade cases whose lesions were of low grade for the most part. MDM2 amplification status was revealed by fluorescence in situ hybridization in all 18 cases; 2 patients—histologically intermediate- and high-grade cases—were found to have MDM2 amplification. In conclusion, this study indicates that histologically low-grade and relatively low-grade cases of ESOS are not always associated with MDM2 amplification. The ESOS case with MDM2 amplification could be high grade, although MDM2-amplified dedifferentiated liposarcoma with osteogenic differentiation should be ruled out in making the diagnosis..
235. Hiroaki Ogata, Yuzo Yamamoto, Taishi Harada, Yoichi Nakanishi, Isamu Okamoto, Eiji Iwama, Eiji Iwama, Koji Kato, Yoshinao Oda, Severe Aplastic Anemia during Osimertinib Therapy in a Patient with EGFR Tyrosine Kinase Inhibitor–Resistant Non–Small Cell Lung Cancer, Journal of Thoracic Oncology, 10.1016/j.jtho.2016.12.023, 12, 5, e46-e47, 2017.05.
236. Kimihiro Tanaka, Eriko Tokunaga, Nami Yamashita, Yasuaki Sagara, Yasuyo Ohi, Kenichi Taguchi, Shinji Ohno, Shinji Okano, Yoshinao Oda, Yoshihiko Maehara, The relationship between the expression of FOXA1 and GATA3 and the efficacy of neoadjuvant endocrine therapy, Breast Cancer, 10.1007/s12282-016-0714-3, 24, 3, 384-392, 2017.05, Background: Estrogen receptor (ER)/GATA3/Forkhead box A1 (FOXA1) network is necessary for the ERα functional signature. High FOXA1 expression indicates a good prognosis in ER-positive breast cancer. However, little is known about the significance of FOXA1 and GATA3 expression in neoadjuvant endocrine therapy (NAE). The aim of this study is to investigate their predictive potential for NAE and their expression changes after NAE. Methods: FOXA1 and GATA3 expression was evaluated using immunohistochemistry in 66 patients with ER-positive/HER2-negative breast cancer who had been treated with NAE. The association between biological marker expressions and the efficacy of NAE and their expression changes after NAE were analyzed. Results: The median pre-treatment FOXA1 and GATA3 expressions were 94.6 and 90 %. Pre-treatment FOXA1 expression was positively correlated with GATA3 (P = 0.0003) and progesterone receptor (PgR) (P = 0.0138). There was no correlation between pre- or post-treatment FOXA1 and GATA3 expressions and the efficacy of NAE. Post-treatment Ki67 expression was significantly lower in tumors with partial response (PR) (P = 0.0007). In terms of the changes of the expression, PgR, Ki67, and FOXA1 expression significantly decreased after NAE (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). Conclusions: FOXA1 and GATA3 expression was not correlated with the efficacy of NAE, but FOXA1 expression was significantly reduced after NAE..
237. Ryutaro Uchi, Yusuke Takahashi, Atsushi Niida, Teppei Shimamura, Hidenari Hirata, Keishi Sugimachi, Genta Sawada, Takeshi Iwaya, Junji Kurashige, Yoshiaki Shinden, Tomohiro Iguchi, Hidetoshi Eguchi, Kenichi Chiba, Yuichi Shiraishi, Genta Nagae, Kenichi Yoshida, Yasunobu Nagata, Hiroshi Haeno, Hirofumi Yamamoto, Hideshi Ishii, Yuichiro Doki, Hisae Iinuma, Shin Sasaki, Satoshi Nagayama, Kazutaka Yamada, Shinichi Yachida, Mamoru Kato, Tatsuhiro Shibata, Eiji Oki, Hiroshi Saeki, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Shizuo Komune, Masaki Mori, Yutaka Suzuki, Ken Yamamoto, Hiroyuki Aburatani, Seishi Ogawa, Satoru Miyano, Koshi Mimori, Erratum
Correction: Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution (PLoS genetics (2016) 12 2 (e1005778)), PLoS genetics, 10.1371/journal.pgen.1006798, 13, 5, e1006798, 2017.05, [This corrects the article DOI: 10.1371/journal.pgen.1005778.]..
238. Toshiya Abe, Kenoki Ouchida, Sho Endo, Fumihiko Ookubo, Yasuhisa Mori, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Ohtsuka Takao, Eishi Nagai, Yoshinao Oda, Masafumi Nakamura, Clinical importance of intraoperative peritoneal cytology in patients with pancreatic cancer, Surgery, 10.1016/j.surg.2016.10.035, 161, 4, 951-958, 2017.04, Background The clinical importance of intraoperative peritoneal cytology in patients with pancreatic cancer remains incompletely understood. Methods Peritoneal washing samples were collected from 411 consecutive patients with pancreatic ductal adenocarcinoma from 1996 to 2014. Of the 411 patients, 335 underwent macroscopically curative resection and 76 with noncurative factors did not undergo resection. We compared long-term outcomes between patients with positive cytology (cytology+) and those with negative cytology (cytology−) and investigated the importance of clinicopathologic factors. Results Of 335 patients with curative resection, 300 (89.6%) were cytology− and 35 (10.4%) were cytology+. The median overall survival of cytology+ patients was less than that of cytology− patients (16 vs 31 months, respectively; P < .0001). The median overall survival of cytology+ patients with noncurative factors was significantly worse than that of cytology+ patients with curative resection (6.9 vs 16.0 months, respectively; P = .0023). The median disease-free survival of cytology+ patients was less than that of cytology− patients (6.5 vs 16 months, respectively; P < .0001). In the multivariate analysis, cytology+ was an independent prognostic factor for overall survival and disease-free survival. Conclusion Cytology+ without noncurative factors was a predictive factor for a poor prognosis. Therefore, it is important to regard patients with pancreatic cancer characterized by cytology+ as a special group that may warrant more aggressive adjuvant therapy..
239. Keijiro Ueda, Ken Kawabe, Lingaku Lee, Yuichi Tachibana, Nao Fujimori, Hisato Igarashi, Yoshinao Oda, Robert T. Jensen, Ryoichi Takayanagi, Tetsuhide Ito, Diagnostic Performance of 48-Hour Fasting Test and Insulin Surrogates in Patients with Suspected Insulinoma, Pancreas, 10.1097/MPA.0000000000000772, 46, 4, 476-481, 2017.04, Objectives This study aimed to evaluate the usefulness of the 48-hour fasting test and insulin surrogates followed by a glucagon stimulatory test (GST) for the diagnosis of insulinoma. Methods Thirty-five patients with suspected insulinoma who underwent 48-hour fasting test and GST were retrospectively included in our study: 15 patients with surgically proven insulinomas and 20 patients in whom insulinoma was clinically ruled out. We determined the duration of the fasting test, plasma glucose levels, serum levels of immunoreactive insulin and C-peptide, and insulin surrogates (serum levels of β-hydroxybutyrate, free fatty acid, and response of plasma glucose to intravenous glucagon [ΔPG]) at the end of the fast. Results The sensitivity and specificity of the 48-hour fasting test were 100.0% and 80.0%, respectively, for the diagnosis of insulinoma. When the 48-hour fasting test and immunoreactive insulin, C-peptide, or insulin surrogates were combined, the combination with GST showed the best results. The sensitivity, specificity, and accuracy rate were 93.3%, 95.0%, and 94.3%, respectively, with 1 false-negative case and 1 false-positive case occurring. Conclusions A more accurate and less invasive diagnosis of insulinoma was possible by combining the 48-hour fasting test with the GST, compared with the existing method..
240. Yuichi Yamada, Masaaki Kuda, Kenichi Kouhashi, Hidetaka Yamamoto, Junkichi Takemoto, Takeaki Ishii, Kunio Iura, Akira Maekawa, Hirofumi Bekki, Takamichi Ito, Hiroshi Otsuka, Makoto Kuroda, Yumi Honda, Shinji Sumiyoshi, Takeshi Inoue, Naoe Kinoshita, Atsushi Nishida, Kyoko Yamashita, Ichiro Ito, Shizuo Komune, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda, Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes, Virchows Archiv, 10.1007/s00428-017-2072-8, 470, 4, 373-380, 2017.04, CIC-DUX4 and BCOR-CCNB3 fusion-gene-associated small round cell sarcomas account for a proportion of pediatric small round cell sarcomas, but their pathological features have not been sufficiently clarified. We reviewed a large number of soft tissue tumors registered at our institution, retrieved the cases of unclassified tumors with a small round cell component, and subjected them to histopathological, immunohistochemical, and gene profile analysis. We reviewed 164 cases of unclassified tumors with a small round cell component and analyzed them by RT-PCR and FISH. Tumors positive for a specific fusion-gene were also subjected to histopathological and immunohistochemical examinations. We identified 16 cases of BCOR-CCNB3/CIC-associated (CIC-DUX4 or CIC gene rearrangement-positive) sarcomas. These included seven BCOR-CCNB3 sarcomas and nine CIC-associated sarcomas. Heterogeneous elements included a myxoid spindle cell component in three BCOR-CCNB3 sarcomas and an epithelioid cell component in two CIC-associated sarcomas (one CIC-DUX4-positive and one CIC-DUX4-negative sarcomas). Mitotic activity was low in both heterogeneous components. By immunohistochemistry, in seven BCOR-CCNB3 sarcomas expression of EMA was positive in two cases, of p63 in three, of CD56 in six, of TLE1 in seven, of NKX2.2 in two, of CCNB3 in seven, and of BCOR in six cases (one case could not be tested for BCOR). In nine cases of CIC-associated sarcoma, CD56 was expressed in five, alpha-smooth muscle actin in one, ERG in three, and CD99, WT1 and TLE1 each in eight cases. Both sarcoma types showed not only a small round cell component, but also a myxoid/epithelioid component with low mitotic activity..
241. Kazuo Adachi, Toshiro Umezaki, Toshimitsu Nishijima, Hidetaka Yamamoto, Yoshinao Oda, Long-term outcomes of type I thyroplasty with silicone implantation
Assessment of excised laryngeal tissue from a patient with secondary hypopharyngeal carcinoma, Auris Nasus Larynx, 10.1016/j.anl.2016.07.007, 44, 2, 245-248, 2017.04, Here we describe the long-term outcomes of type I thyroplasty (TP-I) with silicone block implantation through histopathological assessments in a male patient who underwent pharyngolaryngectomy for secondary hypopharyngeal carcinoma 7 years after silicone implantation. A 66-year-old man presented with esophageal carcinoma and underwent subtotal esophagotomy. Subsequently, his left vocal fold exhibited fixation in a paramedian position, and he underwent TP-I with silicone block implantation 2 years after the primary esophageal surgery. His voice quality improved; however, he developed glottic carcinoma in the right vocal fold 6 months after TP-I and underwent laser cordectomy. Glottic carcinoma recurred 21 months later, and he underwent laser cordectomy again. Five years after the second laser surgery, he underwent pharyngolaryngectomy and neck dissection for hypopharyngeal carcinoma detected in the right pyriform sinus. We histopathologically examined a horizontal section of the resected larynx to assess silicone implant-related changes. Although migration of the silicone implant was not observed, a very mild foreign body reaction occurred around the implant. The patient is currently in remission. Our findings suggest that silicone implants are suitable for TP-I due to their remarkable affinity for human tissue and the low risk of a tissue reaction..
242. Kenichi Kouhashi, Yoshinao Oda, Oncogenic roles of SMARCB1/INI1 and its deficient tumors, Cancer Science, 10.1111/cas.13173, 108, 4, 547-552, 2017.04, SMARCB1/INI1 is one of the core subunit proteins of the ATP-dependent SWI/SNF chromatin remodeling complex, and is identified as a potent and bona fide tumor suppressor. Interactions have been demonstrated between SMARCB1/INI1 and key proteins in various pathways related to tumor proliferation and progression: the p16-RB pathway, WNT signaling pathway, sonic hedgehog signaling pathway and Polycomb pathway. Initially, no detectable SMARCB1/INI1 protein expression was found in malignant rhabdoid tumor cells, whereas all other kinds of tumor cells and non-tumorous tissue showed SMARCB1/INI1 protein expression. Therefore, immunohistochemical testing for the SMARCB1/INI1 antibody has been considered useful in confirming the histologic diagnosis of malignant rhabdoid tumors. However, recently, aberrant expression of SMARCB1/INI1 has been found in various tumors such as epithelioid sarcomas, schwannomatosis, synovial sarcomas, and so on. In addition, it has been reported that aberrant expression can be classified into three patterns: complete loss, mosaic expression and reduced expression. Although the various pathways related to mechanisms of tumorigenesis and tumor proliferation are complexly intertwined, the clarification of these mechanisms may contribute to therapeutic strategies in SMARCB1/INI1-deficient tumors. In terms of pathological classifications, SMARCB1/INI1-deficient tumors may be re-classified by genetic backgrounds..
243. Tanaka K, Tokunaga E, Inoue Y, Yamashita N, Saeki H, Okano S, Kitao H, Oki E, Oda, Y, Maehara Y, The relationship between the expression of FOXA1 and GATA3 and the efficacy of neoadjuvant endocrine therapy., Breast Cancer., 24, 3, 384-392, 2017.03.
244. Iura, Kunio, Maekawa, Akira, Kohashi, Kenichi, Ishii, Takeaki, Bekki, Hirofumi, Otsuka, Hiroshi, Yamada, Yuichi, Yamamoto Hidetaka, Harimaya, Katsumi, Iwamoto, Yukihide, Oda, Yoshinao, Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1, HUMAN PATHOLOGY, 10.1016/j.humpath.2016.12.006, 61, 130-139, 2017.03.
245. Toyokawa G, Takada K, Okamoto T, Kozuma Y, Matsubara T, Haratake N, Akamine T, Takamori S, Katsura M, Shoji F, Hamamoto R, Oda, Yoshinao, Yoshihiko Maehara, Elevated Metabolic Activity on 18F-FDG PET/CT Is Associated with the Expression of EZH2 in Non-small Cell Lung Cancer.
, Anticancer Research, 37, 3, 1393-1401, 2017.03.
246. Hida, Risa, Yamamoto Hidetaka, Hirahashi, Minako, Kumagai, Reiko, Nishiyama, Kenichi, Gi, Toshihiro, Esaki, Motohiro, Kitazono, Takanari, Oda, Yoshinao, Duodenal Neoplasms of Gastric Phenotype An Immunohistochemical and Genetic Study With a Practical Approach to the Classification, AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 41, 3, 343-353, 2017.03.
247. Takada K, Toyokawa G, Okamoto T, Shimokawa M, Kozuma Y, Matsubara T, Haratake N, Akamine T, Takamori S, Katsura M, Shoji F, Oda, Y, Maehara Y, A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non-Small-Cell Lung Cancer Patients.
, Clinical Lung Cancer, 2017.03.
248. Kawamoto M, Onishi H, Ozono K, Yamasaki A, Imaizumi A, Kamakura S, Nakano K, Oda, Y, Sumimoto H, Nakamura M, Tropomyosin-related kinase B mediated signaling contributes to the induction of malignant phenotype of gallbladder cancer., Oncotarget., 10.18632/oncotarget.16063, 8, 22, 36211-36224, 2017.03.
249. Okumura, Takashi, Ohuchida, Kenoki, Sada, Masafumi, Abe, Toshiya, Endo, Sho, Koikawa, Kazuhiro, Iwamoto, Chika, Miura, Daisuke, Mizuuchi, Yusuke, Moriyama, Taiki, Nakata, Kohei, Miyasaka, Yoshihiro, Manabe, Tatsuya, Ohtsuka, Takao, Nagai, Eishi, Mizumoto, Kazuhiro, Oda, Yoshinao, Hashizume, Makoto, Nakamura, Masafumi, Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells, ONCOTARGET, 10.18632/oncotarget.15430, 8, 11, 18280-18295, 2017.03.
250. Tsutsumi S, Saeki H, Nakashima Y, Ito S, Oki E, Morita M, Oda, Yoshinao, Okano S, Maehara Y, PD-L1 expression at tumor invasive front is associated with EMT and poor prognosis in esophageal squamous cell carcinoma.
, Cancer Science, 2017.03.
251. Miyazaki T, Yoshihiro Ohishi et al., Miyasaka Y, Oda Y, Aishima S, Ozono K, Abe A, Nagai E, Nakamura M, Oda, Y, Molecular Characteristics of Pancreatic Ductal Adenocarcinomas with High-Grade Pancreatic Intraepithelial Neoplasia (PanIN) Are Different from Those without High-Grade PanIN.
, Pathobiology, 2017.03.
252. Toyokawa G, Takada K, Okamoto T, Shimokawa M, Kozuma Y, Matsubara T, Haratake N, Takamori S, Akamine T, Katsura M, Shoji F, Oda, Y, Maehara,Y, Computed Tomography Features of Lung Adenocarcinomas With Programmed Death Ligand 1 Expression.
, Clin Lung Cancer, 2017.03.
253. Toyokawa G, Takada K, Okamoto T, Shimokawa M, Kozuma Y, Matsubara T, Haratake N, Takamori S, Akamine T, Katsura M, Shoji F, Oda, Y, Maehara,Y, Computed Tomography Features of Lung Adenocarcinomas With Programmed Death Ligand 1 Expression.
, Clin Lung Cancer, 2017.03.
254. Toyokawa G, Takada K, Okamoto T, Kawanami S, Kozuma Y, Matsubara T, Haratake N, Takamori S, Akamine T, Katsura M, 山田 裕一, Shoji F, Baba S, Kamitani T, Honda H, Oda, Y, Maehara Y, Relevance Between Programmed Death Ligand 1 and Radiologic Invasiveness in Pathologic Stage I Lung Adenocarcinoma.
, Ann Thorac Surg, 2017.03.
255. Gouji Toyokawa, Kazuki Takada, Tatsuro Okamoto, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Ryuji Hamamoto, Yoshinao Oda, Yoshihiko Maehara, Elevated metabolic activity on 18f-fdg pet/ct is associated with the expression of ezh2 in non-small cell lung cancer, Anticancer research, 10.21873/anticanres.11461, 37, 3, 1393-1401, 2017.03, Background/Aim: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in the pathogenesis of lung cancer. We evaluated the metabolic characteristics of non-small cell lung cancer (NSCLC) in patients with and without expression of EZH2 using 18Ffluorodeoxyglucose positron-emission tomography/ computed tomography (18F-FDG PET/CT). Materials and Methods: The EZH2 protein expression of 268 patients with resected NSCLC, whose preoperative 18F-FDG PET/CT information was available, was evaluated by immunohistochemistry with clone 6A10 antibody; cases with Allred score 3 were considered positive. Results: Maximized standard uptake values in cases of EZH2-positive NSCLC and adenocarcinoma were significantly higher in comparison to EZH2-negative cases (p<0.001, and p<0.001, respectively). The expression of EZH2 in NSCLC and adenocarcinoma was associated with significantly poorer survival. Conclusion: In patients with NSCLC and adenocarcinoma, EZH2 positivity was associated with a high uptake of FDG, suggesting that EZH2 might define metabolically malignant lung cancer..
256. Fujita, Nobuhiro, Asayama, Yoshiki, Nishie, Akihiro, Ishigami, Kousei, Ushijima, Yasuhiro, Takayama, Yukihisa, Okamoto, Daisuke, Moirta, Koichiro, Shirabe, Ken, Aishima, Shinichi, Wang, Huanlin, Oda Yoshinao, Honda, Hiroshi, Mass-forming intrahepatic cholangiocarcinoma: Enhancement patterns in the arterial phase of dynamic hepatic CT - Correlation with clinicopathological findings, EUROPEAN RADIOLOGY, 10.1007/s00330-016-4386-3, 27, 2, 498-506, 2017.02.
257. Imada, Kenjiro, Shiota, Masaki, Kuroiwa, Kentaro, Sugimoto, Masaaki, Abe, Tatsuro, Kohashi, Kenichi, Yokomizo, Akira, Eto, Masatoshi, Naito, Seiji, Oda Yoshinao, FOXO3a Expression Regulated by ERK Signaling is Inversely Correlated With Y-Box Binding Protein-1 Expression in Prostate Cancer, PROSTATE, 10.1002/pros.23254, 77, 2, 145-153, 2017.02.
258. Hida T, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, Kawahara K, Iwasaki A, Okamoto T, Oda, Y, Honda H, Nabeshima K, Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry, LUNG CANCER, 10.1016/j.lungcan.2016.12.017, 104, 98-105, 2017.02.
259. Imada, Kenjiro, Shiota, Masaki, Kuroiwa, Kentaro, Sugimoto, Masaaki, Abe, Tatsuro, Kohashi, Kenichi, Yokomizo, Akira, Eto, Masatoshi, Naito, Seiji, Oda, Yoshinao, FOXO3a Expression Regulated by ERK Signaling is Inversely Correlated With Y-Box Binding Protein-1 Expression in Prostate Cancer, PROSTATE, 10.1002/pros.23254, 77, 2, 145-153, 2017.02.
260. Takada K, Okamoto T, Toyokawa G, Kozuma Y, Matsubara T, Haratake N, Akamine T, Takamori S, Katsura M, Shoji F, Oda, Y, Maehara Y, The expression of PD-L1 protein as a prognostic factor in lung squamous cell carcinoma.
, 104, 7-15, 2017.02.
261. Fujimoto, Takaaki, Ohtsuka, Takao, Nakashima, Yohei, Gotoh, Yoshitaka, Date, Kenjiro, Mori, Yasuhisa, Sadakari, Yoshihiko, Takahata, Shunichi, Oda, Yoshinao, Nakamura, Masafumi, Elevated bile amylase level without pancreaticobiliary maljunction is a risk factor for gallbladder carcinoma, JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES, 10.1002/jhbp.421, 24, 2, 103-108, 2017.02.
262. Fujita, Nobuhiro, Asayama, Yoshiki, Nishie, Akihiro, Ishigami, Kousei, Ushijima, Yasuhiro, Takayama, Yukihisa, Okamoto, Daisuke, Moirta, Koichiro, Shirabe, Ken, Aishima, Shinichi, Wang, Huanlin, Oda, Yoshinao, Honda, Hiroshi, Mass-forming intrahepatic cholangiocarcinoma: Enhancement patterns in the arterial phase of dynamic hepatic CT - Correlation with clinicopathological findings, EUROPEAN RADIOLOGY, 10.1007/s00330-016-4386-3, 27, 2, 498-506, 2017.02.
263. Bai Xiaopeng, Tanaka, Yoshimasa, Ihara, Eikichi, Hirano, Katsuya, Nakano, Kayoko, Hirano, Mayumi, Oda, Yoshinao, Nakamura, Kazuhiko, Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body, EUROPEAN JOURNAL OF PHARMACOLOGY, 10.1016/j.ejphar.2017.01.004, 797, 65-74, 2017.02.
264. Yamashita K, Kohashi K, Yamada Y, Nishida Y, Urakawa H, Oda, Y, Toyokuni S, Primary extraskeletal osteosarcoma: a clinicopathological study of 18 cases focusing on MDM2 amplification status.
, Hum Pathol, 2017.02.
265. Mori, Hitomi, Kubo, Makoto, Yamaguchi, Rin, Nishimura, Reiki, Osako, Tomofumi, Arima, Nobuyuki, Okumura, Yasuhiro, Okido, Masayuki, Yamada, Mai, Kai, Masaya, Kishimoto, Junji, Oda, Y, Nakamura, Masafumi, The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer, ONCOTARGET, 10.18632/oncotarget.14698, 8, 9, 15584-15592, 2017.02.
266. Kazuki Takada, Tatsuro Okamoto, Gouji Toyokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara, The expression of PD-L1 protein as a prognostic factor in lung squamous cell carcinoma, Lung Cancer, 10.1016/j.lungcan.2016.12.006, 104, 7-15, 2017.02, Background Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy has become the standard option of care in the management of lung cancer. The expression of the PD-L1 protein in lung cancer is expected to be a prognostic factor or to predict the response to PD-1-blocking antibodies. However, the association between PD-L1 positivity and the clinicopathological features and patient outcomes in lung squamous cell carcinoma (SCC) remains unclear because the definitive cut-off value for the expression of PD-L1 protein remains to be established. Materials and methods The expression of PD-L1 protein in 205 surgically resected primary lung SCC patients was evaluated by immunohistochemistry with the antibody clone SP142. We generated a histogram to show the proportion of PD-L1-positive carcinoma cells, and set the cut-off values as 1%, 5%, 10% and 50%. Moreover, we examined the proliferative capacity of these tumors using Ki-67 immunohistochemistry. Results The samples from 106 (51.7%), 72 (35.1%), 61 (29.7%) and 37 (18.0%) patients were positive for the expression of PD-L1 protein at cut-off values of 1%, 5%, 10% and 50%, respectively. Fisher's exact test showed that, for almost all of the factors, PD-L1 positivity was not associated with the clinicopathological features with any of the four cut-off values. Univariate and multivariate survival analyses revealed that the PD-L1-positive patients only had a poorer prognosis than the PD-L1-negative patients at the 1% cut-off value. The Ki-67 labeling index in the PD-L1-positive patients was higher than that in the PD-L1-negative patients. Conclusions The expression of PD-L1 protein was associated with a poor prognosis in lung SCC patients. The 1% cut-off value for PD-L1 might become a better predictive marker than the other cut-off values..
267. E. Hashimoto, M. Ishikawa, K. Shinoda, M. Hasegawa, H. Komagata, N. Kobayashi, N. Mochidome, Yoshinao Oda, C. Iwamoto, Kenoki Ouchida, M. Hashizume, Tissue classification of liver pathological tissue specimens image using spectral features, SPIE Medical Imaging 2017 Proceedings of SPIE - The International Society for Optical Engineering, 10327, 2017.02.
268. Akiyama, Shingo, Saeki, Hiroshi, Nakashima, Yuichiro, Iimori, Makoto, Kitao, Hiroyuki, Oki, Eiji, Oda Yoshinao, Nakabeppu, Yusaku, Kakeji, Yoshihiro, Maehara, Yoshihiko, Prognostic impact of MutT homolog-1 expression on esophageal squamous cell carcinoma, Auris Nasus Larynx, 10.1002/cam4.979, 6, 1, 258-266, 2017.01.
269. Yoshihiro T, Tsuchihashi K, Kusaba H, Nakashima T, Obara T, Nio K, Takayoshi K, Kodama H, Tsuruta N, Kiyohara H, Asai K, Harada E, Kamezaki K,Arita T,Sato M, Yamamoto H, Arita S, Ariyama H, Harada E, Oda, Y, Akashi K, Cardiac metastasis of squamous cell carcinoma of the thyroid gland with severe disseminated intravascular coagulation: A case report.
, Mol Clin Oncol, 6, 1, 91-95, 2017.01.
270. Nakaji, Yu, Oki, Eiji, Nakanishi, Ryota, Ando, Koji, Sugiyama, Masahiko, Nakashima, Yuichiro, Yamashita, Nami, Saeki, Hiroshi, Oda, Y, Maehara, Yoshihiko, Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 10.1007/s00432-016-2275-4, 143, 1, 151-160, 2017.01.
271. Aso A, Ihara E, Nakamura K, Sudovykh I, Ito T, Nakamura M, Ikeda T, Takizawa N, Oda, Y, Shimizu S, Solid Pseudopapillary Neoplasm of the Pancreas in Young Male Patients: Three Case Reports.
, Case Rep Gastrointest Med, 2017.01.
272. Akiyama, Shingo, Saeki, Hiroshi, Nakashima, Yuichiro, Iimori, Makoto, Kitao, Hiroyuki, Oki, Eiji, Oda, Y, Nakabeppu, Yusaku, Kakeji, Yoshihiro, Maehara, Yoshihiko, Prognostic impact of MutT homolog-1 expression on esophageal squamous cell carcinoma, CANCER MEDICINE, 10.1002/cam4.979, 6, 1, 258-266, 2017.01.
273. Motoshima, Takanobu, Komohara, Yoshihiro, Ma, Chaoya, Dewi, Arni Kusuma, Noguchi, Hirotsugu, Yamada, Sohsuke, Nakayama, Toshiyuki, Kitada, Shohei, Kawano, Yoshiaki, Takahashi, Wataru, Sugimoto, Masaaki, Fujimoto, Naohiro, Oda, Yoshinao, Eto, Masatoshi, PD-L1 expression in papillary renal cell carcinoma, BMC Urology, 10.1186/s12894-016-0195-x, 17, 2017.01.
274. Reiko Miyazaki, Hiroshi Uchi, Takamichi Ito, Takeaki Ishii, Yuichi Yamada, Yoshinao Oda, Masutaka Furue, A case of undifferentiated pleomorphic sarcoma originally diagnosed as dedifferentiated liposarcoma, Nishinihon Journal of Dermatology, 10.2336/nishinihonhifu.79.46, 79, 1, 46-49, 2017.01, A 69-year-old man was referred to us with a 6-month history of a projecting lesion on his back, which had been suspected to be a malignant fibrous histiocytoma based on the results of a needle biopsy. Histopathologically, at the time of a wide resection, the tumor had a clear boundary between the tumoral component and the surrounding adipocytic component, and he was diagnosed as having dedifferentiated liposarcoma. However, reexamination of the case revealed no atypical cells suggesting liposarcoma in the adipose component. Immunohistochemically, the tumor cells were positive for cyclin dependent kinase-4, but negative for murine double minute-2 (MDM2). In addition, fluorescence in situ hybridization failed to reveal the amplification of the MDM2 gene, leading to the final diagnosis of undifferentiated pleomorphic sarcoma..
275. Hiromichi Nakayama, Kenoki Ohuchida, Masaki Yoshida, Tetsuyuki Miyazaki, Shin Takesue, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Takashi Okumura, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Kengo Shirahane, Tatsuya Manabe, Takao Ohtsuka, Hiroki Toma, Yohei Tominaga, Eishi Nagai, Kazuhiro Mizumoto, Yoshinao Oda, Masafumi Nakamura, Degree of desmoplasia in metastatic lymph node lesions is associated with lesion size and poor prognosis in pancreatic cancer patients, Oncology Letters, 10.3892/ol.2017.6549, 14, 3, 3141-3147, 2017.01, Pancreatic cancer is characterized by increased hyperplasia of fibrotic tissue, termed desmoplasia, and lymph node metastasis is an independent prognostic factor in this disease. However, there are no reports focused on desmoplasia in pancreatic cancer lymph node metastases. The present study evaluated a range of factors and investigated their association with poor prognosis in pancreatic cancer cases with lymph node metastasis, including the degree of desmoplasia in lesions. To identify the poor prognostic factors associated with lymph node metastasis, the present study retrospectively reviewed the clinical data of 65 patients with lymph node metastases that underwent surgical pancreatic cancer resection between 2007 and 2012 at a single institution. The investigation focused on the degree of fibrosis in metastatic lesions in 216 lymph nodes, and investigated associations with prognosis or clinicopathological findings. The ratios of the fibrotic area in metastatic lymph node lesions were evaluated and classified into three categories, high (≥70%), moderate (10-70%) and low (<10%). Desmoplasia was not observed in cancer-free lymph nodes. The size of metastatic lymph node lesions was additionally measured, and a significant association between metastatic lesion size and the degree of desmoplasia was observed (P<0.001). The degree of desmoplasia was additionally associated with local extranodal invasion. In the analysis of 65 pancreatic cancer patients with metastatic lymph nodes, the presence of multiple metastatic lymph nodes with moderate or high desmoplasia was significantly associated with poor survival (high, P=0.0048; moderate/high, P=0.0075). Of several clinicopathological factors, the presence of multiple metastatic lymph nodes with high or moderate desmoplasia was associated with overall survival in univariate (P=0.0098) and multivariate (P=0.0466) analyses. The degree of desmoplasia in metastatic lymph nodes is associated with lesion size, and the presence of multiple metastatic lymph nodes with desmoplasia is an independent poor prognostic factor, suggesting that the desmoplasia may have an important role in the malignant progression of lymph node metastases..
276. Risa Hida, Hidetaka Yamamoto, Minako Hirahashi, Reiko Kumagai, Kenichi Nishiyama, Toshihiro Gi, Motohiro Esaki, Takanari Kitazono, Yoshinao Oda, Duodenal Neoplasms of Gastric Phenotype
An Immunohistochemical and Genetic Study with a Practical Approach to the Classification, American Journal of Surgical Pathology, 10.1097/PAS.0000000000000785, 41, 3, 343-353, 2017.01, Duodenal neoplasm of gastric phenotype (DNGP) is very rare, and details of its histopathologic, genetic, and biological features are still unclear. Frequent gene mutations in GNAS, KRAS, and APC have been reported in pyloric gland adenomas and fundic gland-type neoplasms (initially reported as low-grade adenocarcinomas) of the stomach. Here we retrospectively analyzed 16 cases of extra-ampullary DNGP (benign to malignant), and we examined the mucin immunoprofile and oncogene mutations (GNAS, KRAS, APC, BRAF, and CTNNB1). The 16 DNGPs were histologically classified into adenomas (5 pyloric gland adenomas and 2 foveolar-type adenomas), neoplasms of uncertain malignant potential (NUMPs, n=6), and invasive adenocarcinomas (n=3). NUMPs consisted of slightly atypical epithelial cells with pale, eosinophilic, or basophilic cytoplasm growing in an anastomosing or branching glandular pattern, often with expansive submucosal extension. In contrast to invasive adenocarcinomas, NUMPs lacked significant nuclear irregularity, desmoplastic stromal reaction, lymphovascular invasion, and metastasis; their features were reminiscent of fundic gland-type neoplasms of the stomach. Immunophenotypically, most of NUMPs were predominantly positive for MUC6 with variable expressions of pepsinogen-I, H + K + ATPase, human gastric mucin, and MUC5AC. Molecular analyses revealed the gene mutations of GNAS in 6 (38%) of 16 DNGPs (4 [57%] adenomas, 1 [16%] NUMP, and 1 [33%] invasive adenocarcinoma) and APC in 4 of 15 (27%) DNGPs: no adenomas, 2 (33%) NUMPs, and 2 (67%) invasive adenocarcinomas. BRAF mutation was present in only 1 (16%) NUMP, and KRAS and CTNNB1 mutations were absent. In conclusion, gastric-phenotype adenomas and NUMPs of the duodenum are similar to their counterparts of the stomach, in terms of histologic, genetic, and clinicopathologic features. We propose the term "NUMP" as an intermediate category between adenoma and definitely invasive adenocarcinoma. Our findings may provide novel insights into the classification of undescribed but distinctive duodenal tumors showing similarity to gastric-phenotype neoplasms of the stomach..
277. Tomoko Wada, Yoshihiro Ohishi, Tsunehisa Kaku, Murasaki Aman, Hiroko Imamura, Nobuko Yasutake, Kenzo Sonoda, Kiyoko Kato, Yoshinao Oda, Endocervical adenocarcinoma with morphologic features of both usual and gastric types clinicopathologic and immunohistochemical analyses and high-risk hpv detection by in situ hybridization, American Journal of Surgical Pathology, 10.1097/PAS.0000000000000833, 41, 5, 696-705, 2017.01, The fourth edition of the World Health Organization classification set up new entities of endocervical adenocarcinoma (ECA), namely the "usual type" and "gastric type." These 2 types are considered to be distinct histogenetically because of their differing immunophenotypes, human papillomavirus (HPV) status, and prognoses. Usual-Type ECAs (UECAs) are virtually always associated with high-risk human papillomavirus (HR-HPV) infection. Gastric-Type ECAs (G-ECAs) are believed not to be associated with HR-HPV infection. Morphologically, U-ECA cells are characterized by mucin-poor and eosinophilic cytoplasm, resembling endometrioid carcinoma (a pseudoendometrioid feature). G-ECA cells are characterized by abundant clear or pale, mucinous cytoplasm and distinct cell borders. However, in routine practice we noticed that some ECAs contain morphologically usual type- like components and gastric type-like components in a single tumor; we have named these "G+U" ECAs. The histogenesis of such tumors has not been investigated. We conducted the present study to clarify the clinicopathologic and immunohistochemical features and HPV status of G+U ECAs, and to determine whether G+U ECAs are genuine G-ECAs mimicking U-ECAs or genuine U-ECAs with gastric type-like morphology. We retrospectively analyzed a series of 70 consecutive cases of ECA diagnosed as mucinous ECA, endocervical type, and we reclassified them on the basis of the latest World Health Organization classification. We identified 48 (69%) pure U-ECAs, 9 pure G-ECAs, and 13 G+U ECAs. Ten of the 13 G+U ECAs (77%) showed no HR-HPV infection by in situ hybridization (HPV-unrelated G+U ECAs) and showed frequent HIK1083 expression and aberrant p53 expression in both usual type-like and gastric type-like components. The other 3 G+U ECAs showed HR-HPV infection (HPV-related G+U EACs) and frequent p16+/p53-/HIK1083- immunophenotype in both usual type-like and gastric type-like components. The U-ECAs were characterized by HR-HPV infection detected by in situ hybridization and frequent p16+/ p53-/HIK1083- immunophenotype, similar to that of the HPV-related G+U ECAs. In contrast, the pure G-ECAs were characterized by the absence of HPV infection and frequent HIK1083 expression and aberrant p53 expression, similar to that of HPV-unrelated G+U ECAs. G+U ECAs thus represent a heterogenous group composed of genuine G-ECAs and genuine U-ECAs. Most of the G+U ECAs we examined were genuine HPV-unrelated G-ECAs with usual type-like components showing mucin-poor, eosinophilic cytoplasm (pseudoendometrioid morphology). A small population of G+U ECAs was genuine HPV-related U-ECAs with gastric type-like components showing mucin-rich, voluminous cytoplasm. Thus, both types of ECAs can occasionally display patterns of differentiation suggesting a component of the other type but true mixed tumors do not appear to exist. Ancillary techniques (immunohistochemical analysis of p16, p53, and HPV DNA detection assays) should be used to assure proper classification of tumors with mixed morphologic features..
278. Takashi Hatano, Masanobu Ohishi, Goichi Yoshimoto, Moriyasu Yamauchi, Akira Maekawa, Hidetaka Yamamoto, Yoshinao Oda, Makoto Endo, Hirofumi Bekki, Tomoya Matsunobu, Yasuharu Nakashima, Ken Okazaki, Jun Ichi Fukushi, Akiko Oyamada, Yukihide Iwamoto, Methotrexate-related lymphoproliferative disorder presenting with severe swelling of the elbow joint, JBJS case connector, 10.2106/JBJS.CC.17.00002, 7, 3, 2017.01, Case: A patient with rheumatoid arthritis (RA) who was being treated with methotrexate (MTX) therapy presented with severe swelling of the left elbow. Magnetic resonance imaging showed a tumor-like lesion around the elbow joint. Fluorodeoxyglucose positron emission tomography indicated multiple lesions in the lung and the lymph nodes. An open biopsy of a cervical lymph node was performed, and MTX-related lymphoproliferative disorder (MTX-LPD) was diagnosed. After cessation of the MTX therapy, the elbow swelling regressed, and the patient was in remission of MTX-LPD. Conclusion: MTX-LPD should be considered in the differential diagnosis when a patient with RA develops severe joint swelling while on MTX therapy..
279. Nobuhiro Tsuruta, Kotoe Takayoshi, Shuji Arita, Tomomi Aikawa, Hiroshi Ariyama, Hitoshi Kusaba, Kenoki Ohuchida, Eishi Nagai, Kenichi Kohashi, Minako Hirahashi, Kyoko Inadomi, Mamoru Tanaka, Kosuke Sagara, Yuta Okumura, Kenta Nio, Michitaka Nakano, Masafumi Nakamura, Yoshinao Oda, Koichi Akashi, Eishi Baba, Systemic chemotherapy with pronounced efficacy and neutropenia in a granulocyte-colony stimulating factor-producingadvanced gastric neuroendocrine carcinoma, Oncology Letters, 10.3892/ol.2017.6299, 14, 2, 1500-1504, 2017.01, An advanced granulocyte-colony stimulating factor (G-CSF)-producing tumor is rare, and it exhibits leukocytosis in association with high serum G-CSF levels. A 67-year-old male with a 1-month history of bloody emesis and black stools was revealed to exhibit leukocytosis, anemia and a high serum concentration of G-CSF. During a gastrointestinal endoscopy, an ulcerating tumor was identified in the stomach. Computed tomography and a fluorodeoxyglucose-positron emission tomography scan demonstrated direct invasion of the gastric tumor into the transverse colon, regional lymphadenopathy, lung nodules and diffuse high uptake of FDG in bone marrow. The histological diagnosis was a G-CSF-producing neuroendocrine carcinoma (NEC) (tumor 4b, node 2, metastasis 1, pulmonary, clinical stage IV). Systemic chemotherapy consisting of cisplatin and irinotecan was started. Common terminology criteria of adverse events grade 3 tumor lysis syndrome and gastric penetration appeared. Grade 4 neutropenia lasted for 10 days despite intensive G-CSF administration. Prominent shrinkage of the primary and the metastatic tumors was observed subsequent to 3 cycles of chemotherapy. Total gastrectomy and resection of the transverse colon were subsequently performed. Systemic chemotherapy was effective for a G-CSF-producing advanced gastric NEC with careful monitoring and appropriate supportive care for severe adverse events..
280. Tomoaki Taguchi, Satoshi Ieiri, Kina Miyoshi, Kenichi Kohashi, Yoshinao Oda, Akio Kubota, Yoshio Watanabe, Hiroshi Matsufuji, Masahiro Fukuzawa, Takeshi Tomomasa, The incidence and outcome of allied disorders of Hirschsprung's disease in Japan
Results from a nationwide survey, Asian Journal of Surgery, 10.1016/j.asjsur.2015.04.004, 40, 1, 29-34, 2017.01, Background Allied disorders of Hirschsprung's disease (ADHD) have been proposed to be the concept of the functional obstruction of the intestine with the presence of ganglion cells in the terminal rectum. They are classified into two categories based on pathology: (1) abnormal ganglia, including immaturity of ganglia, hypoganglionosis (HG), and intestinal neuronal dysplasia; (2) normal ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS), segmental dilatation (SD), internal anal sphincter achalasia (IASA), and chronic idiopathic intestinal pseudo-obstruction (CIIP). Some of these show poor prognosis, therefore, the establishment of criteria and appropriate treatment strategies is required. Methods The questionnaires were sent to the 161 major institutes of pediatric surgery or gastroenterology in Japan, in order to collect the cases of ADHD during 10 years from 2001 and 2010. Results In total, 355 cases were collected. They included 28 immaturity of ganglia, 130 HG (121 congenital, 9 acquired), 18 intestinal neuronal dysplasia, 33 MMIHS, 43 SD, three IASA, and 100 CIIP. Of the 95 institutes, 69 (72.6%) had their own criteria for ADHD. Criteria were based on clinical symptoms and signs, and conventional pathological examinations. Prognosis was poor in congenital HG, MMIHS, and CIIP, while the others showed good survival rates. Conclusion Almost all Japanese cases of ADHD in the past 10 years were collected. Congenital HG and CIIP showed relatively high incidence, whereas acquired HG and IASA were extremely rare in Japan. The criteria of each disorder were also collected and summarized. Prognosis was poor in congenital HG, MMIHS, and CIIP..
281. Naoki Date, Tsuyoshi Shoji, Yusuke Wakatsuki, Yuichi Yamada, Yoshinao Oda, Hiromichi Katakura, Undifferentiated/unclassified sarcoma in the lung
A case report, Japanese Journal of Lung Cancer, 10.2482/haigan.57.866, 57, 7, 866-869, 2017.01, Background. Primary pulmonary sarcomas are rare tumors, and their differential diagnosis has many branches. Case. A 79-year-old woman was urgently transferred to our institution complaining of hemoptysis. Chest computed tomography revealed a lung tumor measuring 5 cm in size in the central area of the right middle lobe. Bronchoscopy did not provide a definitive diagnosis. We performed right pneumonectomy for the diagnosis and treatment. A histological examination showed the proliferation of round to short spindle-shaped cells with oval nuclei. The tumor was unable to be classified into any well-defined categories due to the lack of distinguishing immunohistochemical features. Ultimately, a diagnosis of undifferentiated/unclassified sarcoma was made. Conclusion. Primary pulmonary sarcomas are very rare, and their differential diagnosis is sometimes difficult..
282. Mori, Hitomi, Kubo, Makoto, Nishimura, Reiki, Osako, Tomofumi, Arima, Nobuyuki, Okumura, Yasuhiro, Okido, Masayuki, Yamada, Mai, Kai, Masaya, Kishimoto, Junji, Miyazaki, Tetsuyuki, Oda Yoshinao, Nakamura, Masafumi, BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer, JAPANESE JOURNAL OF RADIOLOGY, 10.1371/journal.pone.0167016, 11, 12, 2016.12.
283. Shimamatsu, Shinichiro, Okamoto, Tatsuro, Haro, Akira, Kitahara, Hirokazu, Kohno, Mikihiro, Morodomi, Yosuke, Tagawa, Tetsuzo, Okano, Shinji, Oda, Yoshinao, Maehara, Yoshihiko, Prognostic Significance of Expression of the Epithelial-Mesenchymal Transition-Related Factor Brachyury in Intrathoracic Lymphatic Spread of Non-Small Cell Lung Cancer, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-016-5530-7, 23, S1012-S1020, 2016.12.
284. Tanaka K, Tokunaga E, Inoue Y, Yamashita N, Saeki H, Okano S, Kitao H, Oki E, Oda, Yoshinao, Impact of the expression of vimentin and Axl in breast cancer.
, Clinical Breast Cancer, 16, 6, 520-526, 2016.12.
285. Toyokawa G, Takada K, Okamoto T, Kozuma Y, Matsubara T, Haratake N, Takamori S, Akamine T, Katsura M, Shoji F, Oda, Y, Maehara Y, High Frequency of Programmed Death-ligand 1 Expression in Emphysematous Bullae-associated Lung Adenocarcinomas., Clin Lung Cancer., 2016.12.
286. Yoshida, Tsukihisa, Okamoto, Tatsuro, Yano, Tokujiro, Takada, Kazuki, Kohno, Mikihiro, Suda, Kenichi, Takenoyama, Mitsuhiro, Oda, Yoshinao, Maehara, Yoshihiko, Molecular Factors Associated with Pemetrexed Sensitivity According to Histological Type in Non-small Cell Lung Cancer, ANTICANCER RESEARCH, 10.21873/anticanres.11228, 36, 12, 6319-6326, 2016.12.
287. Zheng B, Ohuchida K, Chijiiwa Y, Zhao M, Mizuuchi Y, Cui L, Horioka K, Ohtsuka T, Mizumoto K, Oda, Yoshinao, Hashizume M, Nakamura M, Tanaka M, CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression.
, Mol Carcinog. , 55, 11, 1560-1572, 2016.12.
288. Kimihiro Tanaka, Eriko Tokunaga, Yuka Inoue, Nami Yamashita, Hiroshi Saeki, Shinji Okano, Hiroyuki Kitao, Eiji Oki, Yoshinao Oda, Yoshihiko Maehara, Impact of Expression of Vimentin and Axl in Breast Cancer, Clinical Breast Cancer, 10.1016/j.clbc.2016.06.015, 16, 6, 520-526.e2, 2016.12, The receptor tyrosine kinase Axl has been reported to be a downstream effector of epithelial-to-mesenchymal transition and to be regulated by vimentin expression in preclinical models. Coexistence of vimentin-positive and Axl-high expression was significantly associated with triple-negative breast cancer and poor prognosis. Vimentin and Axl expression might contribute to the aggressive phenotype in breast cancer patients. Background The association between Axl and vimentin protein expression has been observed in several cell lines. However, the clinical importance of Axl and vimentin expression in breast cancer have not been fully determined. Patients and Methods The expressions of Axl and vimentin were evaluated by immunohistochemistry in a total of 343 patients with invasive ductal carcinoma. The relationships between expression of Axl and vimentin and clinicopathologic characteristics and prognosis were analyzed. Results Axl expression was classified into high (n = 170) and low (n = 173) expression groups. Axl expression alone was not associated with any clinicopathologic factor or prognosis. Coexistence of vimentin-positive and Axl-high expression was observed in 10.5% (n = 36). Vimentin-positive and Axl-high tumors were associated with triple-negative breast cancers (P = .0396) and with poor prognosis in terms of both recurrence-free survival (P = .0126) and overall survival (P = .0005) compared to the other groups, including vimentin-positive and Axl-low tumors, vimentin-negative and Axl-high tumors, and vimentin-negative and Axl-low tumors. Multivariate analysis showed that coexistence of vimentin-positive and Axl-high expression was an independent poor prognostic factor for recurrence-free survival (hazard ratio, 2.78; 95% confidence interval, 1.23-5.68; P = .0158) and overall survival (hazard ratio, 3.72; 95% confidence interval, 1.51-8.47; P = .0059). Conclusion Coexistence of vimentin-positive and Axl-high expression is a poor prognostic factor for primary breast cancer. Vimentin and Axl expression might contribute to the aggressive phenotype in breast cancer..
289. Lee JC, Su SY, Changou CA, Yang RS, Tsai KS, Collins MT, Orwoll ES, Lin CY, Chen SH, Shih SR, Lee CH, Oda Y, Billings SD, Li CF, Nielsen GP, Konishi E, Petersson F, Carpenter TO, Huang HY, Comprehensive Characterization of FN1-FGFR1 and Novel FN1-FGF1 Fusion Genes in a Large Series of Phosphaturic Mesenchymal Tumors.
, Mod Pathol., 29, 11, 1335-1346, 2016.11, Phosphaturic mesenchymal tumors typically cause paraneoplastic osteomalacia, chiefly as a result of FGF23 secretion. In a prior study, we identified FN1-FGFR1 fusion in 9 of 15 phosphaturic mesenchymal tumors. In this study, a total of 66 phosphaturic mesenchymal tumors and 7 tumors resembling phosphaturic mesenchymal tumor but without known phosphaturia were studied. A novel FN1-FGF1 fusion gene was identified in two cases without FN1-FGFR1 fusion by RNA sequencing and cross-validated with direct sequencing and western blot. Fluorescence in situ hybridization analyses revealed FN1-FGFR1 fusion in 16 of 39 (41%) phosphaturic mesenchymal tumors and identified an additional case with FN1-FGF1 fusion. The two fusion genes were mutually exclusive. Combined with previous data, the overall prevalence of FN1-FGFR1 and FN1-FGF1 fusions was 42% (21/50) and 6% (3/50), respectively. FGFR1 immunohistochemistry was positive in 82% (45/55) of phosphaturic mesenchymal tumors regardless of fusion status. By contrast, 121 cases of potential morphologic mimics (belonging to 13 tumor types) rarely expressed FGFR1, the main exceptions being solitary fibrous tumors (positive in 40%), chondroblastomas (40%), and giant cell tumors of bone (38%), suggesting a possible role for FGFR1 immunohistochemistry in the diagnosis of phosphaturic mesenchymal tumor. With the exception of one case reported in our prior study, none of the remaining tumors resembling phosphaturic mesenchymal tumor had either fusion type or expressed significant FGFR1. Our findings provide insight into possible mechanisms underlying the pathogenesis of phosphaturic mesenchymal tumor and imply a central role of the FGF1-FGFR1 signaling pathway. The novel FN1-FGF1 protein is expected to be secreted and serves as a ligand that binds and activates FGFR1 to achieve an autocrine loop. Further study is required to determine the functions of these fusion proteins..
290. Sugiyama M, Oki E, Nakaji Y, Tsutsumi S, Ono N, Nakanishi R, Sugiyama M, Nakashima Y, Sonoda H, Ohgaki K, Yamashita N, Saeki H, Okano S, Kitao H, Morita M, Oda, Yoshinao, Maehara Y., High expression of the Notch ligand Jagged-1 is associated with poor prognosis after surgery for colorectal cancer.
, Cancer Sci. , 107, 11, 1705-1716, 2016.11.
291. Biao Zheng, Kenoki Ohuchida, Yoshiro Chijiiwa, Ming Zhao, Yusuke Mizuuchi, Lin Cui, Kohei Horioka, Takao Ohtsuka, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura, Masao Tanaka, CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression, Molecular Carcinogenesis, 10.1002/mc.22409, 55, 11, 1560-1572, 2016.11, Cancer-associated fibroblasts (CAFs) are heterogeneous cell populations that influence tumor initiation and progression. CD146 is a cell membrane protein whose expression has been implicated in multiple human cancers. CD146 expression is also detected in pancreatic cancer stroma; however, the role it plays in this context remains unclear. This study aimed to clarify the function and significance of CD146 expression in pancreatic cancer. We performed immunohistochemical staining to investigate the prevalence of CD146 expression in stromal fibroblasts in pancreatic cancer. We also examined the influence of CD146 on CAF-mediated tumor invasion and migration and CAF activation using CD146 small interfering RNA or overexpression plasmids in primary cultures of CAFs derived from pancreatic cancer tissues. CD146 expression in CAFs was associated with high-grade pancreatic intraepithelial neoplasia and low histological grade invasive ductal carcinoma of the pancreas, while patients with low CD146 expression had a poorer prognosis. Blocking CD146 expression in CAFs significantly enhanced tumor cell migration and invasion in a co-culture system. CD146 knockdown also promoted CAF activation, possibly by inducing the production of pro-tumorigenic factors through modulation of NF-κB activity. Consistently, overexpression of CD146 in CAFs inhibited migration and invasion of co-cultured cancer cells. Finally, CD146 expression in CAFs was reduced by interaction with cancer cells. Our findings suggest that decreased CD146 expression in CAFs promotes pancreatic cancer progression..
292. Yasutaka Mitamura, Shuchi Azuma, Daisuke Matsumoto, Aki Takada-Watanabe, Minoru Takemoto, Koutaro Yokote, Junichi Motoshita, Yoshinao Oda, Masutaka Furue, Satoshi Takeuchi, Case of sarcomatoid carcinoma occurring in a patient with Werner syndrome, Journal of Dermatology, 10.1111/1346-8138.13399, 43, 11, 1362-1364, 2016.11.
293. Jen Chieh Lee, Sheng Yao Su, Chun A. Changou, Rong Sen Yang, Keh Sung Tsai, Michael T. Collins, Eric S. Orwoll, Chung Yen Lin, Shu Hwa Chen, Shyang Rong Shih, Cheng Han Lee, Yoshinao Oda, Steven D. Billings, Chien Feng Li, G. Petur Nielsen, Eiichi Konishi, Fredrik Petersson, Thomas O. Carpenter, Kesavan Sittampalam, Hsuan Ying Huang, Andrew L. Folpe, Characterization of FN1-FGFR1 and novel FN1-FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors, Modern Pathology, 10.1038/modpathol.2016.137, 29, 11, 1335-1346, 2016.11, Phosphaturic mesenchymal tumors typically cause paraneoplastic osteomalacia, chiefly as a result of FGF23 secretion. In a prior study, we identified FN1-FGFR1 fusion in 9 of 15 phosphaturic mesenchymal tumors. In this study, a total of 66 phosphaturic mesenchymal tumors and 7 tumors resembling phosphaturic mesenchymal tumor but without known phosphaturia were studied. A novel FN1-FGF1 fusion gene was identified in two cases without FN1-FGFR1 fusion by RNA sequencing and cross-validated with direct sequencing and western blot. Fluorescence in situ hybridization analyses revealed FN1-FGFR1 fusion in 16 of 39 (41%) phosphaturic mesenchymal tumors and identified an additional case with FN1-FGF1 fusion. The two fusion genes were mutually exclusive. Combined with previous data, the overall prevalence of FN1-FGFR1 and FN1-FGF1 fusions was 42% (21/50) and 6% (3/50), respectively. FGFR1 immunohistochemistry was positive in 82% (45/55) of phosphaturic mesenchymal tumors regardless of fusion status. By contrast, 121 cases of potential morphologic mimics (belonging to 13 tumor types) rarely expressed FGFR1, the main exceptions being solitary fibrous tumors (positive in 40%), chondroblastomas (40%), and giant cell tumors of bone (38%), suggesting a possible role for FGFR1 immunohistochemistry in the diagnosis of phosphaturic mesenchymal tumor. With the exception of one case reported in our prior study, none of the remaining tumors resembling phosphaturic mesenchymal tumor had either fusion type or expressed significant FGFR1. Our findings provide insight into possible mechanisms underlying the pathogenesis of phosphaturic mesenchymal tumor and imply a central role of the FGF1-FGFR1 signaling pathway. The novel FN1-FGF1 protein is expected to be secreted and serves as a ligand that binds and activates FGFR1 to achieve an autocrine loop. Further study is required to determine the functions of these fusion proteins..
294. Kazuki Takada, Tatsuro Okamoto, Fumihiro Shoji, Mototsugu Shimokawa, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Yuzo Suzuki, Takatoshi Fujishita, Gouji Toyokawa, Yosuke Morodomi, Shinji Okano, Yoshinao Oda, Yoshihiko Maehara, Clinical significance of PD-L1 protein expression in surgically resected primary lung adenocarcinoma, Journal of Thoracic Oncology, 10.1016/j.jtho.2016.06.006, 11, 11, 1879-1890, 2016.11, Introduction: The clinicopathological features of carcinomas expressing programmed death ligand 1 (PD-L1) and their associations with common driver mutations, such as mutations in the EGFR gene, in lung adenocarcinoma are not clearly understood. Here, we examined PD-L1 protein expression in surgically resected primary lung adenocarcinoma and the association of PD-L1 protein expression with clinicopathological features, EGFR mutation status, and patient outcomes. Methods: The expression of PD-L1 protein in 417 surgically resected primary lung adenocarcinomas was evaluated by immunohistochemical analysis. The cutoff value for defining PD-L1 positivity was determined according to the histogram of proportions of PD-L1-positive cancer cells. Results: Samples from 85 patients (20.4%) and 144 patients (34.5%) were positive for PD-L1 protein expression according to 5% and 1% PD-L1 cutoff values, respectively. Fisher's exact tests showed that PD-L1 positivity was significantly associated with male sex, smoking, higher tumor grade, advanced T status, advanced N status, advanced stage, the presence of pleural and vessel invasions, micropapillary or solid predominant histological subtypes, and wild-type EGFR. Univariate and multivariate survival analyses revealed that patients with PD-L1 positivity had poorer prognoses than those without PD-L1 protein expression at the 1% cutoff value (disease-free survival p < 0.0001, overall survival p < 0.0001). Conclusions: PD-L1 protein expression was significantly higher in smoking- A ssociated adenocarcinoma and in EGFR mutation-negative adenocarcinoma. PD-L1 protein expression was associated with poor survival in patients with lung adenocarcinoma. The PD-L1/programmed cell death 1 pathway may contribute to the progression of smokingassociated tumors in lung adenocarcinoma..
295. Minoru Fujino, Shinichi Aishima, Koji Shindo, Yasunori Oda, Katsuya Morimatsu, Kosuke Tsutsumi, Takao Otsuka, Masao Tanaka, Yoshinao Oda, Expression of glucose transporter-1 is correlated with hypoxia-inducible factor 1α and malignant potential in pancreatic neuroendocrine tumors, Oncology Letters, 10.3892/ol.2016.5092, 12, 5, 3337-3343, 2016.11, The present study aimed to investigate the prognostic usefulness of the expression of glucose transporter type 1 (GLUT-1) and GLUT-2, hypoxia-inducible factor 1α (HIF-1α) and insulin-like growth factor II messenger RNA-binding protein 3 (IMP3) in pancreatic neuroendocrine tumors (pNETs). Immunohistochemical staining for GLUT-1, GLUT-2, HIF-1α and IMP3 was performed in 70 pNET specimens. The expression of GLUT-1 and HIF-1α was significantly higher in the World Health Organization grade 2 (G2), neuroendocrine carcinoma cases and mixed-type pNETs compared with the G1 cases. Vessel invasion, a high Ki-67 labeling index and a high mitotic count were significantly more frequent in the GLUT-1- and HIF-1α-positive cases compared with the negative cases. Lymph node metastasis was significantly higher in the GLUT-1-positive cases than in the negative cases. Insulin expression was significantly higher in the IMP3-positive cases than the negative cases. The GLUT-1 expression group experienced a significantly poor disease-free survival rate compared with the negative GLUT-1 expression group. HIF-1α expression was significantly correlated with poor disease-free survival and overall survival rates. A multivariate analysis revealed that lymph node metastasis was an independent risk factor for disease-free survival in all cases. In the G1/G2 group, tumor size and lymph node metastasis were independent risk factors for disease-free survival. Overall, the results suggested that GLUT-1 is a useful prognostic biomarker for pNETs..
296. Masakazu Sugiyama, Eiji Oki, Yu Nakaji, Satoshi Tsutsumi, Naomi Ono, Ryota Nakanishi, Masahiko Sugiyama, Yuichiro Nakashima, Hideto Sonoda, Kippei Ohgaki, Nami Yamashita, Hiroshi Saeki, Shinji Okano, Hiroyuki Kitao, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara, High expression of the Notch ligand Jagged-1 is associated with poor prognosis after surgery for colorectal cancer, Cancer Science, 10.1111/cas.13075, 107, 11, 1705-1716, 2016.11, The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged-1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E-cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse-free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E-cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E-cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E-cadherin expression. In vitro studies suggested that RAS-MEK-MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC..
297. Hida, Tomoyuki, Hamasaki, Makoto, Matsumoto, Shinji, Sato, Ayuko, Tsujimura, Tohru, Kawahara, Kunimitsu, Iwasaki, Akinori, Okamoto, Tatsuro, Yoshinao Oda, Honda, Hiroshi, Nabeshima, Kazuki, BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests, PATHOLOGY INTERNATIONAL, 10.1111/pin.12453, 66, 10, 563-570, 2016.10.
298. Kohashi K, Tanaka Y, Kishimoto H, Yamamoto H, Yamada Y, Taguchi T, Iwamoto Y, Oda Y, Reclassification of rhabdoid tumor and pediatric undifferentiated/unclassified sarcoma with complete loss of SMARCB1/INI1 protein expression: three subtypes of rhabdoid tumor according to their histological features, MODERN PATHOLOGY, 10.1038/modpathol.2016.106, 29, 10, 1232-1242, 2016.10.
299. Fujita, Nobuhiro, Nishie, Akihiro, Asayama, Yoshiki, Ishigami, Kousei, Ushijima, Yasuhiro, Takayama, Yukihisa, Okamoto, Daisuke, Shirabe, Ken, Yoshizumi, Tomoharu, Kotoh, Kazuhiro, Furusyo, Norihiro, Hida, Tomoyuki, Oda Yoshinao, Fujioka, Taisuke, Honda, Hiroshi, Fibrosis in nonalcoholic fatty liver disease: Noninvasive assessment using computed tomography volumetry, WORLD JOURNAL OF GASTROENTEROLOGY, 10.3748/wjg.v22.i40.8949, 22, 40, 8949-8955, 2016.10.
300. Asayama Y, Nishie A, Ishigami K, Ushijima Y, Takayama Y, Okamoto D, Fujita N, Ohtsuka T, Yoshizumi T, Aishima S, Oda, Y, Honda H, Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma.
, Eur Radiol, 2016.10.
301. Takizawa, Katsumi, Yamamoto, Hidetaka, Taguchi, Kenichi, Ohno, Shinji, Tokunaga, Eriko, Yamashita, Nami, Kubo, Makoto, Nakamura, Masafumi, Oda Y, Insulin-like growth factor II messenger RNA-binding protein-3 is an indicator of malignant phyllodes tumor of the breast, HUMAN PATHOLOGY, 10.1016/j.humpath.2016.04.007, 55, 30-38, 2016.09.
302. Yamada, Yuichi, Yamamoto Hidetaka, Kohashi Kenichi, Ishii, Takeaki, Iura, Kunio, Maekawa, Akira, Bekki, Hirofumi, Otsuka, Hiroshi, Yamashita, Kyoko, Tanaka, Hiroyuki, Hiraki, Tsubasa, Mukai, Munenori, Shirakawa, Atsuko, Shinnou, Yoko, Jinno, Mari, Yanai, Hiroyuki, Taguchi, Kenichi, Maehara, Yoshihiko, Iwamoto, Yukihide, Histological spectrum of angiofibroma of soft tissue: histological and genetic analysis of 13 cases, HISTOPATHOLOGY, 10.1111/his.12943, 69, 3, 459-469, 2016.09.
303. Abe, Toshiya, Ohuchida, Kenoki, Miyasaka, Yoshihiro, Ohtsuka, Takao, Oda Yoshinao, Nakamura, Masafumi, Comparison of Surgical Outcomes Between Radical Antegrade Modular Pancreatosplenectomy (RAMPS) and Standard Retrograde Pancreatosplenectomy (SPRS) for Left-Sided Pancreatic Cancer, WORLD JOURNAL OF SURGERY, 10.1007/s00268-016-3526-x, 40, 9, 2267-2275, 2016.09.
304. Sonoda K, Yahata H, Okugawa K, Kaneki E, Nakatsuki K, Naka M, Terado N, Ookubo F, Kaku T, Oda, Y, Kato K, Isthmic-vaginal cytological findings after trachelectomy for early-stage cervical cancer.
, Cytopathology, 2016.09.
305. Fujimoto T, Ohtsuka T, Date K, Kimura H, Matsunaga T, Tamura K, Mori Y, Miyasaka Y, Mochidome N, Oda Yoshinao, Nakamura M, Expression of Bcl-2 19-kD interracing protein 3 predicts prognosis after the resection of ampullary carcinoma.
, J Hepatobiliary Pancreat Sci, 23, 8, 489-496, 2016.08.
306. Kimura, Hideyo, Ohtsuka, Takao, Fujimoto, Takaaki, Date, Kenjiro, Matsunaga, Taketo, Cases, Ana Ines, Abe, Atsushi, Mizuuchi, Yusuke, Miyasaka, Yoshihiro, Ito, Tetsuhide, Oda Yoshinao, Nakamura, Masafumi, Tanaka, Masao, Different Hormonal Expression Patterns Between Primary Pancreatic Neuroendocrine Tumors and Metastatic Sites, PANCREAS, 10.1097/MPA.0000000000000570, 45, 7, 947-952, 2016.08.
307. Toyokawa, Gouji, Takada, Kazuki, Haratake, Naoki, Takamori, Shinkichi, Akamine, Takaki, Katsura, Masakazu, Fujishita, Takatoshi, Shoji, Fumihiro, Okamoto, Tatsuro, Oda, Y, Maehara Y, Favorable Disease-free Survival Associated with Programmed Death Ligand 1 Expression in Patients with Surgically Resected Small-cell Lung Cancer, ANTICANCER RESEARCH, 36, 8, 4329-4336, 2016.08.
308. Adachi K, Umezaki T, Nishijima T, Yamamoto H, Oda, Y, Long-term outcomes of type I thyroplasty with silicone implantation: Assessment of excised laryngeal tissue from a patient with secondary hypopharyngeal carcinoma., Auris Nasus Larynx, 2016.08.
309. Masaru Morita, Hiroshi Saeki, Yu Nakaji, Yoko Zaitsu, Minako Hirahashi, Takayuki Ohguri, Eiji Oki, Yasushi Toh, Yoshinao Oda, Yoshihiko Maehara, Conversion to neuroendocrine carcinoma from squamous cell carcinoma of the esophagus after definitive chemoradiotherapy, Anticancer research, 36, 8, 4045-4049, 2016.08, Background/Aim: Neuroendocrine carcinoma (NEC) of the esophagus is rare and aggressive. We herein report a case of a patient who showed NEC conversion from squamous cell carcinoma (SCC) of the esophagus in the recurrent lesion after definitive chemoradiotherapy. Case Report: The patient was a 57-year-old Japanese male with mid-thoracic esophageal carcinoma diagnosed as SCC with invasion of the submucosal layer. After definitive chemoradiotherapy, the esophageal tumor completely disappeared. Two months later, local recurrence was recognized at the same location and salvage surgery was performed. An immunohistochemical examination of the resected specimen revealed that most of the recurrent tumor had neuroendocrine (NE) differentiation, although a retrospective review of the initial biopsy specimen showed no involvement of NE differentiation. Conclusion: This case is significant not only in bringing attention to the possibility of NEC conversion from SCC after chemoradiotherapy, but also in discussing tumors originating in the esophagus..
310. Takaaki Fujimoto, Takao Ohtsuka, Kenjiro Date, Hideyo Kimura, Taketo Matsunaga, Yasuhisa Mori, Yoshihiro Miyasaka, Naoki Mochidome, Yoshinao Oda, Masafumi Nakamura, Expression of Bcl-2 19-kDa interacting protein 3 predicts prognosis after ampullary carcinoma resection, Journal of Hepato-Biliary-Pancreatic Sciences, 10.1002/jhbp.367, 23, 8, 489-496, 2016.08, Background: An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC. Methods: The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated. Results: The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC. Conclusions: BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens..
311. Gouji Toyokawa, Kazuki Takada, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Masakazu Katsura, Takatoshi Fujishita, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara, Favorable disease-free survival associated with programmed death ligand 1 expression in patients with surgically resected small-cell lung cancer, Anticancer research, 36, 8, 4329-4336, 2016.08, Background: The prognostic significance of programmed death ligand 1 (PD-L1) has been reported in non-small cell lung cancer; however, the significance of PDL1 expression in patients with resected small-cell lung cancer (SCLC) remains to be clarified. Materials and Methods: Forty patients with SCLC whose resected specimens were available for immunohistochemistry for PDL1 were evaluated to determine the association between its expression and the clinicopathological factors and prognosis. Results: Among 40 patients, PD-L1 was expressed in tumor cells (TCs) of six (15%), tumor-infiltrating cells (ICs) of 16 (40%), and TCs and/or ICs cells of 18 (45%) patients. Patients with PD-L1-positve ICs and TCs and/or ICs exhibited significantly longer disease-free survival than those without PD-L1-expression (hazard ratio (HR)=0.268; 95% confidence interval (CI)=0.100-0.645; p=0.003 and HR=0.301; 95% CI=0.118-0.702; p=0.005, respectively). Conclusion: This study provides important evidence on the prognostic value of the PD-L1 expression in resected SCLC patients..
312. Naoko Wada, Takamichi Ito, Hiroshi Uchi, Takeshi Nakahara, Gaku Tsuji, Yuichi Yamada, Yoshinao Oda, Masutaka Furue, Superficial CD34-positive fibroblastic tumor
A new case from Japan, Journal of Dermatology, 10.1111/1346-8138.13327, 43, 8, 934-936, 2016.08, A 48-year-old Japanese woman presented with a painless, slow-growing, brown nodule of 15 mm in diameter on the left thigh. She noticed the nodule a few years before the first presentation to our hospital. She underwent total resection of the nodule. On histopathological examination, a relatively well-defined tumor with infiltrative growth was located in the dermis and extended into the subcutis. The tumor was composed of spindle to polygonal cells with pleomorphic nuclei arranged in a sheet-like or fascicular pattern. Tumor cells with granular cytoplasm were also scattered. Immunohistochemical examination revealed that the tumor cells were strongly positive for CD34. The fusion transcripts of the collagen type 1 alpha 1 platelet-derived growth factor beta chain were not detected. After excluding other fibroblastic tumors through histopathological and immunohistochemical examinations, a diagnosis of superficial CD34-positive fibroblastic tumor (SCPFT) was made. SCPFT is a recently proposed fibroblastic tumor that is characterized by striking pleomorphism, granular cytoplasm, low mitotic rate and diffuse CD34 expression. Only two reports with 20 cases have been reported so far. The present case is the first that corresponds to SCPFT in Japan..
313. Fujino M, Aishima S, Shindo K, Oda Y, Motimatsu K, Tsutsumi K, Otsuka T, Tanaka M, Yoshinao Oda, Expression of Glucose transporter-1 is correlated with HIF-1alpha and malignant potential in pancreatic neuroendocrine tumors., Oncology Letters, 12, 3337-3343, 2016.07.
314. Ito T, Kenichi Kohashi, Yamada Y, Maekawa A, Kuda M, Furue M, Yoshinao Oda, Prognostic significance of Forkhead Box M1 (FOXM1) expression and antitumor effect of FOXM1 inhibition in melanoma.
, Histopathology, 69, 1, 63-71, 2016.07.
315. Maekawa, Akira, Kenichi Kohashi, Kuda, Masaaki, Iura, Kunio, Ishii, Takeaki, Endo, Makoto, Nakatsura, Tetsuya, Iwamoto, Yukihide, Oda Yoshinao, Prognostic significance of FOXM1 expression and antitumor effect of FOXM1 inhibition in synovial sarcomas, BMC CANCER, 10.1186/s12885-016-2542-4, 16, 2016.07.
316. Takada K, Toyokawa G, Okamoto T, Akamine T, Takamori S, Katsura M, Fujishita T, Shoji F, Oda Y, Maehara Y, An Immunohistochemical Analysis of PD-L1 Protein Expression in Surgically Resected Small Cell Lung Cancer Using Different Antibodies and Criteria., ANTICANCER RESEARCH, 36, 7, 3409-3412, 2016.07.
317. Yamamoto Hidetaka, Yoshida, Akihiko, Taguchi, Kenichi, Kohashi, Kenichi, Hatanaka, Yui, Yamashita, Atsushi, Mori, Daisuke, Oda Yoshinao, ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours, HISTOPATHOLOGY, 10.1111/his.12910, 69, 1, 72-83, 2016.07.
318. Kimura, T., Wang, L., Tabu, K., Tsuda, M., Tanino, M., Maekawa, A., Nishihara, H., Hiraga, H., Taga, T., Oda Y, Tanaka, S, Identification and analysis of CXCR4-positive synovial sarcoma-initiating cells, ONCOGENE, 10.1038/onc.2015.461, 35, 30, 3932-3943, 2016.07.
319. Shinkai, Kentaro, Nakano, Kenji, Cui, Lin, Mizuuchi, Yusuke, Onishi, Hideya, Oda, Yoshinao, Obika, Satoshi, Tanaka, Masao, Katano, Mitsuo, Nuclear expression of Y-box binding protein-1 is associated with poor prognosis in patients with pancreatic cancer and its knockdown inhibits tumor growth and metastasis in mice tumor models, INTERNATIONAL JOURNAL OF CANCER, 10.1002/ijc.30075, 139, 2, 433-445, 2016.07.
320. Tamura, Koji, Ohtsuka, Takao, Date, Kenjiro, Fujimoto, Takaaki, Matsunaga, Taketo, Kimura, Hideyo, Watanabe, Yusuke, Miyazaki, Tetsuyuki, Ohuchida, Kenoki, Takahata, Shunichi, Ishigami, Kousei, Oda, Yoshinao, Mizumoto, Kazuhiro, Nakamura, Masafumi, Tanaka, Masao, Distinction of Invasive Carcinoma Derived From Intraductal Papillary Mucinous Neoplasms From Concomitant Ductal Adenocarcinoma of the Pancreas Using Molecular Biomarkers, PANCREAS, 45, 6, 826-835, 2016.07.
321. Kyoko Inadomi, Hozumi Kumagai, Shuji Arita, Nobuhiro Tsuruta, Kotoe Takayoshi, Koji Mishima, Shun Ichiro Ota, Mamoru Tanaka, Yuta Okumura, Kosuke Sagara, Kenta Nio, Michitaka Nakano, Hiroshi Uchi, Hidetaka Yamamoto, Hiroshi Ariyama, Hitoshi Kusaba, Hiroaki Niiro, Yoshinao Oda, Koichi Akashi, Eishi Baba, Bi-cytopenia possibly induced by anti-PD-1 antibody for primary malignant melanoma of the esophagus A case report, Medicine (United States), 10.1097/MD.0000000000004283, 95, 29, 2016.07, Background: Anti-programmed cell death 1 antibody nivolumab is a promising agent for various cancers. Immune-related adverse events are recognized; however, bi-cytopenia with nivolumab has not been reported. Case presentation: A 73-year-old man was diagnosed with advanced primary malignant melanoma of the esophagus with liver, lung, and lymph node metastases. Previous therapies including dacarbazine and radiation of 39 Gy to the esophageal region were performed, but the liver metastases deteriorated. The patient was then administered nivolumab (2 mg/kg, every 3 weeks). After 3 cycles, the esophageal tumor and lymph nodes showed marked reductions in size, the lung metastases disappeared, and the liver metastases shrank partially. The treatment continued with 7 cycles for 4 months. However, severe anemia and thrombocytopenia appeared in the 6th cycle, and intermittent blood transfusions were required. The patient received high-dose intravenous methylprednisolone therapy for bi-cytopenia, but it was ineffective. Seven months after the initiation of nivolumab, the patient died of tumor. Although the mechanisms of bi-cytopenia were unclear, it could have been induced by nivolumab. Conclusion: The present case shows a rare but serious life-threatening bi-cytopenia possibly associated with nivolumab and suggests the importance of awareness of hematological adverse events during nivolumab therapy..
322. Koji Tamura, Takao Ohtsuka, Kenjiro Date, Takaaki Fujimoto, Taketo Matsunaga, Hideyo Kimura, Yusuke Watanabe, Tetsuyuki Miyazaki, Kenoki Ohuchida, Shunichi Takahata, Kousei Ishigami, Yoshinao Oda, Kazuhiro Mizumoto, Masafumi Nakamura, Masao Tanaka, Distinction of Invasive Carcinoma Derived from Intraductal Papillary Mucinous Neoplasms from Concomitant Ductal Adenocarcinoma of the Pancreas Using Molecular Biomarkers, Pancreas, 10.1097/MPA.0000000000000563, 45, 6, 826-835, 2016.07, Objectives To clarify the usefulness of molecular biomarkers for distinguishing invasive carcinoma derived from intraductal papillary mucinous neoplasms (IPMNs [Inv-IPMN]) from concomitant pancreatic ductal adenocarcinoma (PDAC). Methods Data from 19 patients with resected concomitant PDAC were retrospectively reviewed. KRAS/GNAS mutations and immunohistochemical (IHC) expression of p53 and p16/CDKN2A were assessed in both IPMN and distinct PDAC. As controls, KRAS/GNAS mutations and IHC labeling were assessed between invasive and noninvasive components in 1 lesion of 22 independent patients. Results KRAS/GNAS mutation status of invasive and noninvasive components in Inv-IPMN was consistent in 18 (86%) of 21 patients. Conversely, mutational patterns in IPMN and distinct PDAC in the same pancreas differed from each other in 17 (89%) of 19. There were 10 (53%) and 8 (42%) of 19 patients who showed the same p53 and p16/CDKN2A staining between concomitant PDAC and distinct IPMN. In the Inv-IPMN cohort, 19 (86%) of 22 patients showed the same IHC expression pattern between the noninvasive and invasive components. Conclusions It may be possible to distinguish Inv-IPMN from concomitant PDAC by assessing these molecular biomarkers. More precise distinction of Inv-IPMN and concomitant PDAC will lead to adequate recognition of the natural history of IPMNs and hence optimal management..
323. Takamichi Ito, Kenichi Kohashi, Yuichi Yamada, Akira Maekawa, Masaaki Kuda, Masutaka Furue, Yoshinao Oda, Prognostic significance of forkhead box M1 (FoxM1) expression and antitumour effect of FoxM1 inhibition in melanoma, Histopathology, 10.1111/his.12909, 69, 1, 63-71, 2016.07, Aims: Forkhead box M1 (FoxM1) is a transcription factor that regulates cell-cycle progression and tumour progression, but limited information is available regarding its clinical significance in melanoma. The aim of this study was to investigate the potency of FoxM1 as a therapeutic target in melanoma. Methods and results: We investigated 60 melanoma clinical samples and a melanoma WM266-4 cell line using immunohistochemical staining and molecular biological approaches. Patients with a FoxM1-overexpressing melanoma had significantly shorter survival [both for melanoma-specific survival (MSS) and disease-free survival (DFS)] than the other patients (P < 0.001, respectively). The FoxM1 overexpression was also an adverse prognostic factor for both MSS and DFS on the Cox multivariate analyses [hazard ratio (HR): 3.96, 95% confidence interval (CI): 1.12–14.27, P = 0.032; HR: 3.21, 95% CI: 1.08–9.67, P = 0.037, respectively). FoxM1 inhibition using siRNA and an inhibitor (thiostrepton) each suppressed the cell proliferation of the melanoma cell line. Furthermore, FoxM1 inhibition improved chemosensitivity to dacarbazine, whereas it reduced cell migration and invasion. These results suggest that FoxM1 plays important roles in tumour progression and the chemoresistance of melanoma. Conclusion: We have shown the prognostic impact of FoxM1 on melanoma patients. FoxM1 inhibition may be a potential therapeutic option for advanced melanoma..
324. Ito T, Uchi H, Nakahara T, Tsuji G, Oda Y, Hagihara A, Furue M, Cutaneous angiosarcoma of the head and face: a single-center analysis of treatment outcomes in 43 patients in Japan, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 10.1007/s00432-016-2151-2, 142, 6, 1387-1394, 2016.06.
325. Kohno, Yukiko, Yamamoto, Hidetaka, Hirahashi, Minako, Kumagae, Yoshiteru, Nakamura, Masafumi, Oki, Eiji, Oda Y, Reduced MUTYH, MTH1, and OGG1 expression and TP53 mutation in diffuse-type adenocarcinoma of gastric cardia, HUMAN PATHOLOGY, 10.1016/j.humpath.2016.01.006, 52, 145-152, 2016.06.
326. Takada K, Okamoto T, Shoji F, Shimokawa M, Akamine T, Takamori S, Katsura M, Suzuki Y, Fujishita T, Toyokawa G, Morodomi Y, Okano S, Oda Y, Maehara Y, Clinical Significance of PD-L1 Protein Expression in Surgically Resected Primary Lung Adenocarcinoma.
, J Thorac Oncol, 11, 11, 1879-1890, 2016.06.
327. Hisamatsu, Yuichi, Oki, Eiji, Otsu, Hajime, Ando, Koji, Saeki, Hiroshi, Tokunaga, Eriko, Aishima, Shinichi, Morita, Masaru, Oda Yoshinao, Maehara, Yoshihiko, Effect of EGFR and p-AKT Overexpression on Chromosomal Instability in Gastric Cancer, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-016-5097-3, 23, 6, 1986-1992, 2016.06.
328. Miyasaka, Yoshihiro, Ohtsuka, Takao, Tamura, Koji, Mori, Yasuhisa, Shindo, Koji, Yamada, Daisuke, Takahata, Shunich, Ishigami, Kousei, Ito, Tetsuhide, Tokunaga, Shoji, Oda Yoshinao, Mizumoto, Kazuhiro, Nakamura, Masafumi, Tanaka, Masao, Predictive Factors for the Metachronous Development of High-risk Lesions in the Remnant Pancreas After Partial Pancreatectomy for Intraductal Papillary Mucinous Neoplasm, ANNALS OF SURGERY, 10.1097/SLA.0000000000001368, 263, 6, 1180-1187, 2016.06.
329. Nio K, Higashi D, Kumagai H, Arita S, Shirakawa T, Nakashima K, Shibata Y, Esaki M, Manabe T, Nagai S,Ueki T, Nakano M, Ariyama H, Kusaba H, Hirahashi M, Oda Y, Esaki T, Mitsugi K, Futami K, Akashi K, Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.
, Anticancer Drugs., 27, 5, 457-463, 2016.06.
330. Kenta Nio, Daijiro Higashi, Hozumi Kumagai, Shuji Arita, Tsuyoshi Shirakawa, Koji Nakashima, Yoshihiro Shibata, Motohiro Esaki, Tatsuya Manabe, Shuntaro Nagai, Takashi Ueki, Michitaka Nakano, Hiroshi Ariyama, Hitoshi Kusaba, Minako Hirahashi, Yoshinao Oda, Taito Esaki, Kenji Mitsugi, Kitaro Futami, Koichi Akashi, Eishi Baba, Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan, Anti-cancer drugs, 10.1097/CAD.0000000000000338, 27, 5, 457-463, 2016.06, Chemotherapy for advanced colitis-associated colorectal cancer (CAC) has been insufficiently evaluated. The goal of this study was to clarify the efficacy and safety of chemotherapy for CAC in Japan. CAC patients who were treated with chemotherapy between 2005 and 2015 were retrospectively examined. Twenty-nine patients (median age, 48 years; 23 men) were assessed. Eighteen patients had ulcerative colitis, and 11 had Crohn's disease. Three ulcerative colitis and four Crohn's disease patients were in the active disease phase. Primary tumors were located in the rectum/anus (n = 16), the left colon (n = 9), or the right colon (n = 4). Palliative or adjuvant chemotherapy was performed in 13 and 16 patients, respectively. First-line palliative chemotherapy regimens were as follows: fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n = 6), FOLFOX + bevacizumab (n = 3), and others (n = 4). Adjuvant chemotherapy regimens were S-1 (n = 7), oxaliplatin-based (n = 4) and others (n = 5). In palliative chemotherapy, the objective response rate was 15%, and the median progression-free survival and overall survival were 182 and 315 days, respectively. In adjuvant chemotherapy, the 5-year relapse-free survival rate was 78%. Grade 3/4 adverse events (AEs) were observed in 16 patients (55%). Active and remission inflammatory bowel disease patients suffered grade 3/4 nonhematological AEs at an incidence of 71 and 23%, respectively (P< 0.01). Dose reduction was required in 11 patients (38%), eight of whom required it for hematological AEs. Adjuvant chemotherapy for CAC exhibited sufficient efficacy, whereas modest efficacy was shown for palliative chemotherapy for CAC. AEs, particularly nonhematological AEs, were closely associated with disease activity of colitis..
331. K. Tahara, K. Yamashita, A. Hiwatashi, O. Togao, K. Kikuchi, M. Endo, H. Otsuka, Y. Oda, H. Honda, MR Imaging Findings of a Leiomyosarcoma of the Thoracic Spine
A Case Report, Clinical Neuroradiology, 10.1007/s00062-015-0420-0, 26, 2, 229-233, 2016.06, We report a case of leiomyosarcoma of the thoracic spine. Primary leiomyosarcoma is a malignant connective tissue tumor originating from smooth muscle cells. Leiomyosarcoma frequently occurs in the uterus, retroperitoneal space, gastrointestinal tract, and deep soft tissues; primary leiomyosarcoma of the bone is rare. The MR imaging including intravoxel incoherent motion (IVIM) imaging findings of the current case indicated a low diffusion coefficient and high blood flow, which were in concurrence with high cell density on histology and increased vascularity by angiography. Although some benign tumors such as osteoblastoma and giant cell tumor would show similar findings on IVIM imaging, these additional imaging features may narrow the differential diagnosis of spinal tumors..
332. Yuma Motomatsu, Yasuhisa Oishi, Shogo Matsunaga, Hirofumi Onitsuka, Hidetaka Yamamoto, Eiko Zaitsu, Yuichi Yamada, Kenichi Kohashi, Yoshinao Oda, Ryuji Tominaga, Primary Cardiac T-Cell Lymphoma Localized in the Mitral Valve, Annals of Thoracic Surgery, 10.1016/j.athoracsur.2015.08.091, 101, 6, 2363-2365, 2016.06, Primary cardiac lymphoma is a rare cardiac tumor, and usually originates from B cells and involves the right side of the heart. We present an extremely rare case of primary cardiac T-cell lymphoma involving the mitral valve alone. A 58-year-old woman who was positive for human T-cell leukemia virus 1 underwent mitral valve replacement because of severe mitral regurgitation. The postoperative pathologic diagnosis of the mitral valve was T-cell lymphoma. Further evaluation revealed no malignancy, except for the mitral valve. To the best of our knowledge, this is the first case of primary cardiac T-cell lymphoma localized in the mitral valve..
333. Iwama Eiji, Koichi Takayama, Harada T, Okamoto Isamu, Fumihiko Ookubo, Junji Kishimoto, Eishi Baba, Yoshinao Oda, Yoichi Nakanishi, Highly sensitive and quantitative detection of EGFR T790M mutations in tumor samples by Nanofluidic Digital PCR.
, 2016.05.
334. Shinkai K, Kenji Nakano, Cui L, Mizuuchi Y, Hideya Onishi, Yoshinao Oda, Obika S, Masao Tanaka, Mitsuo Katano, Nuclear expression of Y-box binding protein-1 is associated with poor prognosis in patients with pancreatic cancer and its knockdown inhibits tumor growth and metastasis in mice tumor models., Int J Cancer, 2016.05.
335. Kinuko Nagayoshi, Takashi Ueki, Tatsuya Manabe, Taiki Moriyama, Kosuke Yanai, Yoshinao Oda, Masao Tanaka, Laparoscopic lateral pelvic lymph node dissection is achievable and offers advantages as a minimally invasive surgery over the open approach, Surgical endoscopy, 10.1007/s00464-015-4418-0, 30, 5, 1938-1947, 2016.05, Background: Laparoscopic lateral pelvic lymph node dissection (LPLD) is a minimally invasive alternative to open surgical therapy for advanced low rectal cancer patients. This study assessed potential risk factors for lateral pelvic lymph node metastasis (LPLM) and evaluated the feasibility and oncological safety of laparoscopic LPLD compared with the conventional open approach. Methods: We retrospectively reviewed the clinical records of 90 patients with advanced low rectal cancer who underwent LPLD following total mesorectal excision at Kyushu University Hospital between January 2001 and July 2014. We compared the clinicopathological features between the patients with and without LPLM and the surgical outcomes between patients who underwent laparoscopic LPLD (LL) and open LPLD (OL). Results: Fourteen (15.6 %) patients had LPLM. Univariate analysis revealed that undifferentiated cancer, positive lymphatic invasion, >50 % circumferential cancer extent, mesorectal lymph node metastases (MLM), and distant metastasis were associated with LPLM. In the multivariate analysis, MLM was the only independent risk factor for LPLM. Forty-six (51.1 %) patients underwent LL, and 44 (48.9 %) patients underwent OL. The mean surgical duration was longer in the LL group than in the OL group (641.0 vs. 312.0 min, P < 0.001). The LL group also had less hemorrhage (252.0 vs. 815.0 mL, P < 0.001) and a shorter hospital stay (22.9 vs. 29.1 days, P = 0.04) than the OL group. The mean number of harvested lateral pelvic lymph nodes was larger in the LL group than in the OL group (19.5 vs. 15.8, P < 0.05). The morbidity rate and overall survival (3-year OS: 94.7 vs. 82.9 %, P = 0.25) did not differ between the two groups. Conclusions: Patients with advanced low rectal cancer presenting MLM are good candidates for LPLD. Laparoscopic LPLD enables retrieval of more lymph nodes and may be acceptable for the treatment of advanced low rectal cancer..
336. Ishii, Takeaki, Kenichi Kohashi, Iura, Kunio, Maekawa, Akira, Bekki, Hirofumi, Yamada, Yuichi, Kohashi K, Yamamoto H, Kumagai R, Yamada Y, Hotokebuchi Y, Taguchi T, Iwa, Nabeshima, Kazuki, Kawashima, Hiroyuki, Hiroyuki; Iwamoto, wamoto, Yukihide, Yoshinao Oda, Activation of the Akt-mTOR and MAPK pathways in dedifferentiated liposarcomas, TUMOR BIOLOGY, 10.1007/s13277-015-4232-2, 37, 4, 4767-4776, 2016.04.
337. Ito T, Tsuji G, Ohno F, Uchi H, Nakahara T, Hashimoto-, Hachiya A,, Yoshida Y, Yamamoto O, Oda Y, Furue M, Activation of the OVOL1-OVOL2 axis in the hair bulb and in pilomatricoma and pilomatrix carcinoma., Am J Pathol, 186, 4, 1036-1043, 2016.04.
338. Kuda, Masaaki, Kenichi Kohashi, Yamada, Yuich, Maekawa, Akira, Kinoshita, Yoshiaki, Nakatsura, Tetsuya, Oda  Yoshinao, FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target, TUMOR BIOLOGY, 10.1007/s13277-015-4351-9, 37, 4, 5213-5223, 2016.04.
339. Tanaka, Yuki, Aishima, Shinichi, Kohashi Kenichi, Okumura, Yukihiko, Wang, Huanlin, Hida, Tomoyuki, Kotoh, Kazuhiro, Shirabe, Ken, Maehara, Yoshihiko, Takayanagi, Ryoichi, Oda Y, Spalt-like transcription factor 4 immunopositivity is associated with epithelial cell adhesion molecule expression in combined hepatocellular carcinoma and cholangiocarcinoma, HISTOPATHOLOGY, 10.1111/his.12806, 68, 5, 693-701, 2016.04.
340. Chijiiwa, Yoshiro, Moriyama, Taiki, Ohuchida, Kenoki, Nabae, Toshinaga, Ohtsuka, Takao, Miyasaka, Yoshihiro, Fujita, Hayato, Maeyama, Ryo, Manabe, Tatsuya, Abe, Atsushi, Mizuuchi, Yusuke, Oda Yoshinao, Mizumoto, Kazuhiro, Nakamura, Masafumi, Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL, INTERNATIONAL JOURNAL OF ONCOLOGY, 10.3892/ijo.2016.3389, 48, 4, 1688-1700, 2016.04.
341. Horioka K, Ouchida K, Sada M, Zheng B, Moriyama T, Fujita H, Manabe T, Ohtsuka T, Shimamoto M, Miyazaki T, Mizumoto K, Oda Yoshinao, Nakamura M, Supression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer.
, Int J Oncol, 48, 4, 2016.04.
342. Komori K, Nakamura K, Ihara E, Iwasa T, Hirahashi M, Oda Y, Yakayanagi R, Endoscopic Submucosal Dissection is Feasible for Very Elderly Patients with Early Gastric Cancer Comparison of Short-Term and Long-Term Outcomes in Very Elderly and Non-elderly Patients.
, Fukuoka Acta Med., 107, 4, 72-81, 2016.04.
343. Nakamura K, Osada M, Goto A, Iwasa T, Takahashi S, Takizawa N, Akahoshi K, Ochiai T, Nakamura N, Akiho H, Itaba S, Harada N, Iju M, Tanaka M, Kubo H, Somada S, Ihara E, Oda Y, Ito T, Short- and long-term outcomes of endoscopic resection of rectal neuroendocrine tumors: analyses according to the WHO 2010 classification.
, Scand J Gastroenterol. , 51, 4, 448-455, 2016.04.
344. Nakano T, Yamamoto H, Nakashima T, Nishijima T, Satoh M, Hatanaka Y, Shiratsuchi H, Yasumatsu R, Toh S, Komune S, Oda Y, Molecular subclassification determined by human papillomavirus and EGFR status is associated with the prognosis of oropharyngeal squamous cell carcinoma., Hum Pathol. 2016 Apr;50:51-61., 50, 51-61, 2016.04.
345. Suyama K, Onishi H, Imaizumi A, Shinkai K, Umebayashi M, Kubo M, Mizuuchi Y, Oda, Yoshinao, Tanaka M, Nakamura M, Katano M, CD24 suppresses malignant phenotype by downregulation of SHH transcription through STAT1 inhibition in breast cancer cells, CANCER LETTERS, 10.1016/j.canlet.2015.12.013, 374, 1, 44-53, 2016.04.
346. Tanaka, Kazuhiro, Hasegawa, Tadashi, Nojima, Takayuki, Oda, Yoshinao, Mizusawa, Junki, Fukuda, Haruhiko, Iwamoto, Yukihide, Prospective evaluation of Ki-67 system in histological grading of soft tissue sarcomas in the Japan Clinical Oncology Group Study JCOG0304, WORLD JOURNAL OF SURGICAL ONCOLOGY, 10.1186/s12957-016-0869-6, 14, 2016.04.
347. Tokunaga R, Imamura Y, Nakamura K, Ishimoto T, Nakagawa S, Miyake K, Nakaji Y, Tsuda Y, Iwatsuki M, Baba Y, Sakamoto Y, Miyamoto Y, Saeki H, Yoshida N, Oki E, Watanabe M, Oda, Y, Bass AJ, Maehara Y, Fibroblast growth factor receptor 2 expression, but not its genetic amplification, is associated with tumor growth and worse survival in esophagogastric junction adenocarcinoma., Oncotarget., 7, 15, 19748-19761, 2016.04.
348. Takamichi Ito, Gaku Tsuji, Fumitaka Ohno, Hiroshi Uchi, Takeshi Nakahara, Akiko Hashimoto-Hachiya, Yuichi Yoshida, Osamu Yamamoto, Yoshinao Oda, Masutaka Furue, Activation of the OVOL1-OVOL2 axis in the hair bulb and in pilomatricoma, American Journal of Pathology, 10.1016/j.ajpath.2015.12.013, 186, 4, 1036-1043, 2016.04, OVOL1 and OVOL2, ubiquitously conserved genes encoding C2H2 zinc finger transcription factors in mammals, control epithelial cell proliferation, and differentiation, including those in skin. OVOL1 and OVOL2 expression is coordinately mediated via the Wnt signaling pathway, and OVOL1 negatively regulates OVOL2 expression in a transcriptional manner. Our previous study of OVOL1 expression in human skin revealed that OVOL1 is preferentially expressed in the inner root sheath of the hair follicle. Therefore, we hypothesized that the OVOL1-OVOL2 axis is involved in normal and neoplastic follicular differentiation. Immunohistochemical analysis showed that OVOL1 and OVOL2 were strongly expressed in a mutually exclusive manner in the cytoplasm of inner root sheath cells and matrix cells, respectively, in normal follicles. OVOL2 was also expressed in pilomatricoma, with only partial expression of OVOL1. Cultured human keratinocytes expressed OVOL1 and OVOL2 on both the mRNA and protein levels. The expression of OVOL2 was higher in keratinocytes transfected with siRNA of OVOL1. Ketoconazole, a hair growth stimulant, up-regulated the expression of OVOL1 but did not affect OVOL2 expression. These results indicated that the OVOL1-OVOL2 axis may actively contribute to cell differentiation and proliferation in the hair bulb, suggesting that the OVOL1 and OVOL2 may be therapeutic targets of hair disorders, including alopecia, and play important roles in the tumorigenesis of pilomatricoma..
349. Keishi Komori, Kazuhiko Nakamura, Eikichiet Ihara, Tsutomu Iwasa, Minako Hirahashi, Yoshinao Oda, Ryoichi Takayanagi, Endoscopic Submucosal Dissection is Feasible for Very Elderly Patients with Early Gastric Cancer
Comparison of Short-Term and Long-Term Outcomes in Very Elderly and Non-Elderly Patients, Fukuoka igaku zasshi = Hukuoka acta medica, 107, 4, 72-81, 2016.04, Background/Aims: Endoscopic submucosal dissection (ESD) has become a standard procedure for the resection of early gastric cancer (EGC). However, the feasibility of ESD for very elderly patients, aged ≥ 80 years, has not been determined.
Methodology: The study population included 67 non-elderly (NE) patients aged ≤ 65 years (80 lesions) and 22 very elderly (VE) patients ≥ 80 years (26 lesions) with EGC who underwent ESD and met the criteria for absolute or expanded indications. Eighteen patients (18 lesions) who underwent ESD but did not meet the criteria for absolute and expanded indications were defined as the outside the indications (OI) group.
Results: En bloc and complete resection rates were excellent in both the VE and NE groups, without differing significantly. Although the rates of ischemic heart disease and antithrombotic agent use were higher in the VE than in the NE group, procedure-related complication rates did not differ significantly. Of the seven very elderly patients in the OI group, two underwent additional gastrectomy, and the other five were followed-up without surgery. No patient in any group experienced local recurrence, metastasis or disease-specific death.
Conclusions: Short- and long-term outcomes of ESD for VE patients with EGC were favorable and did not differ significantly from outcomes in NE patients. ESD may therefore be a good therapeutic option for both VE and NE patients with EGC..
350. Ryuma Tokunaga, Yu Imamura, Kenichi Nakamura, Takatsugu Ishimoto, Shigeki Nakagawa, Keisuke Miyake, Yu Nakaji, Yasuo Tsuda, Masaaki Iwatsuki, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Hiroshi Saeki, Naoya Yoshida, Eiji Oki, Masayuki Watanabe, Yoshinao Oda, Adam J. Bass, Yoshihiko Maehara, Hideo Baba, Fibroblast growth factor receptor 2 expression, but not its genetic amplification, is associated with tumor growth and worse survival in esophagogastric junction adenocarcinoma, Oncotarget, 10.18632/oncotarget.7782, 7, 15, 19748-19761, 2016.04, Background: Fibroblast growth factor receptor 2 (FGFR2) genetic alterations lead to tumor cell proliferation in various types of cancer. We hypothesized that FGFR2 amplification is associated with FGFR2 expression, resulting in tumor growth and poorer outcome in esophagogastric junction (EGJ) adenocarcinoma. Patients and methods: A total of 176 consecutive chemo-naive patients with EGJ adenocarcinoma were enrolled from two academic institutions. FGFR2 amplification was examined by real-time PCR (N = 140) and FGFR2 expression with immunohistochemical staining (N = 176), and compared against clinicopathological factors and patient outcomes. The effects of FGFR2 inhibition or overexpression on cell proliferation, cell cycle, and apoptosis assays were investigated in EGJ adenocarcinoma cell lines. Downstream FGFR2, AKT and ERK were also examined. Results: Based on the correlation between FGFR2 levels and FGFR2 overexpression in vitro, FGFR2 amplification was defined as copy number > 3.0. In clinical samples, FGFR2 amplification and FGFR2 IHC expression were 15% and 61%, respectively. Although these two statuses were significantly correlated (P < 0.05), only FGFR2 IHC expression was significantly associated with tumor depth (multivariate P < 0.001) and overall survival of patients (univariate P = 0.007). Supporting these findings, FGFR2 overexpression was associated with tumor cell proliferation, cell cycle progression, and anti-apoptosis. Selective inhibition of FGFR2 sufficiently suppressed tumor cell proliferation through de-phosphorylation of AKT and ERK. Conclusion: FGFR2 amplification was significantly associated with FGFR2 expression. FGFR2 expression (but not FGFR2 amplification) was associated with tumor growth and patient outcomes. Our findings support FGFR2 as a novel therapeutic target for EGJ adenocarcinoma..
351. Takafumi Nakano, Hidetaka Yamamoto, Torahiko Nakashima, Toshimitsu Nishijima, Masanobu Satoh, Yui Hatanaka, Hideki Shiratsuchi, Ryuji Yasumatsu, Satoshi Toh, Shizuo Komune, Yoshinao Oda, Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma, Human Pathology, 10.1016/j.humpath.2015.11.001, 50, 51-61, 2016.04, Summary Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P =.0026 and P =.0026) and nonkeratinizing histology (P =.0002 and P =.0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P =.0667) and worse overall survival (P <.0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P <.0001 and P <.0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy..
352. Kazuhiko Nakamura, Mikako Osada, Ayako Goto, Tsutomu Iwasa, Shunsuke Takahashi, Nobuyoshi Takizawa, Kazuya Akahoshi, Toshiaki Ochiai, Norimoto Nakamura, Hirotada Akiho, Soichi Itaba, Naohiko Harada, Moritomo Iju, Munehiro Tanaka, Hiroaki Kubo, Shinichi Somada, Eikichi Ihara, Yoshinao Oda, Tetsuhide Ito, Ryoichi Takayanagi, Short- and long-term outcomes of endoscopic resection of rectal neuroendocrine tumours
Analyses according to the WHO 2010 classification, Scandinavian Journal of Gastroenterology, 10.3109/00365521.2015.1107752, 51, 4, 448-455, 2016.04, Objective Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications. Material and methods One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria. The clinicopathological features of these lesions were analysed, and the short- and long-term outcomes of endoscopic resection were evaluated. Results Of the 170 rectal NETs, 166 were histopathologically diagnosed as NET G1 and four as NET G2. Thirty-eight tumours (22.4%) were positive for lymphovascular invasion, a percentage higher than expected. Although the curative resection rate was low (65.3%), en bloc (98.8%) and complete (85.9%) resection rates were high. Modified endoscopic mucosal resection (88.0%) and endoscopic submucosal dissection (92.2%) resulted in significantly higher complete resection rates than conventional endoscopic mucosal resection (36.4%). No patient experienced tumour recurrence, despite the low curative resection rate. Conclusion Despite the low curative resection rate, prognosis after endoscopic resection of rectal NETs was excellent. Prospective large-scale, long-term studies are required to determine whether NET G2 and tumours >1 cm should be included in the indication for endoscopic resection and whether tumours with lymphovascular invasion can be followed up without additional surgery..
353. Kohei Horioka, Kenoki Ohuchida, Masafumi Sada, Biao Zheng, Taiki Moriyama, Hayato Fujita, Tatsuya Manabe, Takao Ohtsuka, Masaya Shimamoto, Tetsuyuki Miyazaki, Kazuhiro Mizumoto, Yoshinao Oda, Masafumi Nakamura, Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer, International journal of oncology, 10.3892/ijo.2016.3374, 48, 4, 1499-1508, 2016.04, Pancreatic stellate cells (PSCs) enhance the malignant behavior of pancreatic cancer by interacting with cancer cells and producing extracellular matrix (ECM). To date, several stroma-targeted therapies for pancreatic cancer have been attempted, but these therapies are still not in practical use. Integrins expressed in stromal cells are involved in fibrosis of several organs, as well as promoting tumor malignancy. We investigated whether CD51, also known as integrin αV, expressed in PSCs was associated with stromal formation of pancreatic cancer and enhancement of tumor malignancy. We also assessed the effects of suppression of CD51 in PSCs on pancreatic cancer. Immunohistochemistry for CD51 in resected pancreatic cancer tissues showed that high expression of CD51 in the tumor stroma was associated with lymph node metastasis (P=0.025), positive pathologic margin (P=0.025), and shorter patient survival times (P=0.043). Lentivirus-mediated short hairpin RNA knockdown of CD51 decreased the proliferation and migration of PSCs. Quantitative real-time polymerase chain reaction showed that expression levels of genes related with ECM and tumor-stromal interactions were decreased by CD51 knockdown in PSCs. In a co-implantation model of pancreatic cancer cells and PSCs, tumor growth in vivo was inhibited by CD51 knockdown in PSCs (P<0.05). We also found reduced tumor stroma and decreased proliferation of cancer cells in implanted cancer tissues with CD51-silenced PSCs (P<0.05). Our results showed that CD51 expression in pancreatic cancer stroma is associated with enhanced tumor malignancy and that CD51 may be a potential therapeutic target for pancreatic cancer..
354. Sugimoto, Masaaki, Kenichi Kohashi, Kuroiwa, Kentaro, Abe, Tatsuro, Yamada, Yuichi, Masaki Shiota, Imada, Kenjiro, Seiji Naito, Yoshinao Oda, Renal cell carcinoma with rhabdoid-like features lack intracytoplasmic inclusion bodies and show aggressive behavior, VIRCHOWS ARCHIV, 10.1007/s00428-015-1885-6, 468, 3, 357-367, 2016.03.
355. Toomine, Yukie, Sumiko Watanabe, Setsuo Sugishima, Yoshihiro Ohishi et al., Tamiya, Sadafumi, Kobayashi, Hiroaki, Kenzo Sonoda, Yoshinao Oda, Kato Kiyoko, Tsunehisa Kaku, Diagnostic Value of Squamous Cell Change Associated With Endometrial Carcinoma: A Cytopathologic Approach, DIAGNOSTIC CYTOPATHOLOGY, 10.1002/dc.23418, 44, 3, 187-194, 2016.03.
356. Sada M, Ohuchida Kenoki, Horioka K, Okumura T, Moriyama T, Yoshihiro Miysakaka, Ohtsuka Takao, Mizumoto Kazuhiro, Yoshinao Oda, Masafumi Nakamura, Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility.
, Cancer Lett. , 372, 2, 210-218, 2016.03.
357. Kunio Iura, Yoshinao Oda, Genetic Aberration and Pathological Diagnosis in Bone and Soft-Tissue Tumors, Japanese Journal of Cancer and Chemotherapy, 43, 3, 300-304, 2016.03, Bone and soft-tissue sarcomas comprise a rare, complex, and heterogeneous group of tumors for which it is difficult for even experienced pathologists to provide a conclusive diagnosis. The number of diagnoses made using genetic analysis has increased since the detection of fusion genes in several soft-tissue tumors in the 1990s. Moreover, other specific genetic aberrations have been reported in various bone and soft-tissue tumors. In addition, molecular therapeutic targets have been sought in advanced cases of soft-tissue and bone tumors similar to other organ malignancies. To enable the pathological diagnosis of bone and soft-tissue tumors, it is necessary to combine histological diagnosis with immunohistochemistry and gene analysis findings including fusion gene or other genetic aberrations. In this review, we describe the fusion genes recently reported in bone and soft-tissue tumors such as solitary fibrous tumor, aneurysmal bone cyst, nodular fasciitis, CIC-DUX4 fusion gene-positive small round cell tumors, or BCOR-CCNB3-positive sarcoma as well as other genetic aberrations in dedifferentiated liposarcoma, malignant rhabdoid tumor, cartilaginous tumor, Langerhans cell histiocytosis chondroblastoma, or giant cell tumor of the bone. We also demonstrate their association with pathological diagnosis..
358. Kunio Lura, Yoshinao Oda, Genetic aberration and pathological diagnosis in bone and soft-tissue tumors, Japanese Journal of Cancer and Chemotherapy, 43, 3, 300-304, 2016.03, Bone and soft-tissue sarcomas comprise a rare, complex, and heterogeneous group of tumors for which it is difficult for even experienced pathologists to provide a conclusive diagnosis. The number of diagnoses made using genetic analysis has increased since the detection of fusion genes in several soft-tissue tumors in the 1990s. Moreover, other specific genetic aberrations have been reported in various bone and soft-tissue tumors. In addition, molecular therapeutic targets have been sought in advanced cases of soft-tissue and bone tumors similar to other organ malignancies. To enable the pathological diagnosis of bone and soft-tissue tumors, it is necessary to combine histological diagnosis with immunohistochemistry and gene analysis findings including fusion gene or other genetic aberrations. In this review, we describe the fusion genes recently reported in bone and soft-tissue tumors such as solitary fibrous tumor, aneurysmal bone cyst, nodular fasciitis, CIC-DUX4 fusion gene-positive small round cell tumors, or BCOR-CCNB3-positive sarcoma as well as other genetic aberrations in dedifferentiated liposarcoma, malignant rhabdoid tumor, cartilaginous tumor, Langerhans cell histiocytosis chondroblastoma, or giant cell tumor of the bone. We also demonstrate their association with pathological diagnosis..
359. Masafumi Sada, Kenoki Ohuchida, Kohei Horioka, Takashi Okumura, Taiki Moriyama, Yoshihiro Miyasaka, Takao Ohtsuka, Kazuhiro Mizumoto, Yoshinao Oda, Masafumi Nakamura, Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility, Cancer Letters, 10.1016/j.canlet.2016.01.016, 372, 2, 210-218, 2016.03, Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture. Microarray analysis revealed that procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Stromal PLOD2 expression in surgical specimens of pancreatic cancer was confirmed by immunohistochemistry. RNA interference-mediated knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3-D matrices, leading to decreased directional migration of cancer cells within the matrices. In conclusion, these findings indicate that hypoxia-induced PLOD2 expression in PSCs creates a permissive microenvironment for migration of cancer cells through architectural regulation of stromal ECM in pancreatic cancer..
360. Fujimori, Nao, Osoegawa, Takashi, Lee, Lingaku, Tachibana, Yuichi;, Aso, Akira, Kubo, Hiroaki, Kawabe, Ken, Igarashi, Hisato, Kazuhiko Nakamura, Yoshinao Oda, Tetsuhide Ito, Efficacy of endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors, SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 10.3109/00365521.2015.1083050, 51, 2, 245-252, 2016.02.
361. Tokunaga, Eriko, Nami Yamashita, Hiroyuki Kitao, Tanaka, Kimihiro, Taketani, Kenji, Inoue, Yuka, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Yoshihiko Maehara, Biological and clinical significance of loss of heterozygosity at the INPP4B gene locus in Japanese breast cancer, BREAST, 10.1016/j.breast.2015.10.006, 25, 62-68, 2016.02.
362. Uchi, Ryutaro, Takahashi, Yusuke;, Niida, Atsushi, Shimamura, Teppei, Hirata, Hidenari, Sugimachi, Keishi, Sawada, Genta, Iwaya, Takeshi, Kurashige, Junji, Shinden, Yoshiaki, Iguchi, Tomohiro, Hidetoshi Eguchi, Chiba, Kenichi;, Shiraishi, Yuichi, Nagae, Genta, Yoshida, Kenichi, Yoshinao Oda, Yoshihiko Maehara, Miyano, Satoru, Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution, PLOS GENETICS, 10.1371/journal.pgen.1005778, 12, 2, 2016.02.
363. Kimura K, Itoh S, Kurihara T, Yoshida Y, Wang H, Harimoto Norifumi, Akihiro Nishie, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Predictors of Benign Status in Liver Tumors Under 3 cm in Diameter Misdiagnosed as Hepatocellular Carcinoma.
, Anticancer Res. , 36, 2, 793-797, 2016.02.
364. 牛島 智基, Tanoue, Yoshihisa, Ide, Tomomi, Okano, Shinji, Yoshinao Oda, Tominaga, Ryuji, Disuse Atrophy of the Aortic Valve After Left Ventricular Assist Device Implantation, ANNALS OF THORACIC SURGERY, 10.1016/j.athoracsur.2015.03.047, 101, 2, 742-744, 2016.02.
365. Koichi Kimura, Shinji Itoh, Takeshi Kurihara, Yoshihiro Yoshida, Huanlin Wang, Norifumi Harimoto, Akihiro Nishie, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Predictors of Benign Status in Liver Tumors Under 3 cm in Diameter Misdiagnosed as Hepatocellular Carcinoma, Anticancer research, 36, 2, 793-797, 2016.02, BACKGROUND: The clinical features of benign liver lesions misdiagnosed as hepatocellular carcinoma have not been fully described.
PATIENTS AND METHODS: This study included 187 patients who underwent hepatectomy at the Kyushu University Hospital following a diagnosis of solitary HCC of ≤3 cm in diameter.
RESULTS: Following hepatectomy, 9.6% patients were pathologically diagnosed with benign liver lesions. Univariate analysis showed that patient age ≤67 years, negativity for hepatitis C virus antigen, lesion size ≤1.5 cm, normal level of tumor markers, and absence of increase in tumor size were associated with benign lesions. Patient age ≤67 years and absence of tumor size increase were independent predictors of benign lesions.
CONCLUSION: Benign liver lesions misdiagnosed as HCC were not infrequent, accounting for approximately 10% of resected cases. Age ≤67 years and absence of tumor size increase were independent predictors of benign liver lesions, and may help in the correct diagnosis of HCC..
366. Yoshihiro Ohishi et al., Hiroko Imamura, Murasaki Aman, Kaai Shida, Tsunehisa Kaku, Kato K, Yoshinao Oda, Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma?, INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, 10.1097/PGP.0000000000000211, 35, 1, 56-65, 2016.01.
367. Ikegami, Koji, Nakamura, Shotaro, Esaki, Motohiro, Yanai, Shunichi, Minako Hirahashi, Yoshinao Oda, Takeshita, Morishige, Matsumoto, Takayuki, Kitazono, Takanari, Prognostic value of chromosomal translocations in small-bowel diffuse large B-cell lymphoma, HISTOPATHOLOGY, 10.1111/his.12731, 68, 2, 199-209, 2016.01.
368. Amamoto, Rie, Takeshi Uchiumi, Mikako Yagi, Monji, Keisuke, Song, YooHyun, Yoshinao Oda, Masaki Shiota, Akira Yokomizo, Naito, Seiji, Kang, Dongchon, The Expression of Ubiquitous Mitochondrial Creatine Kinase Is Downregulated as Prostate Cancer Progression, JOURNAL OF CANCER, 10.7150/jca.13207, 7, 1, 50-59, 2016.01.
369. Maekawa, Akira, Kenichi Kohashi, Setsu, Nokitaka, Kuda, Masaaki, Iura, Kunio, Ishii, Takeaki, Matsunobu, Tomoya, Nakatsura, Tetsuya, Yukihide Iwamoto, Yoshinao Oda, Expression of Forkhead box M1 in soft tissue leiomyosarcoma: Clinicopathologic and invitro study using a newly established cell line, CANCER SCIENCE, 10.1111/cas.12846, 107, 1, 95-102, 2016.01.
370. Takayoshi, Kotoe, Ariyama Hiroshi, Tamura, Shingo, Yoda, Shunsuke, Takeshi Arita, Yamaguchi, Toshihiro, Ozono, Keigo, Yamamoto H, Inadomi, Kyoko, Kumagai, Hozumi, Tanaka, Mamoru, Okumura, Yuta, Sagara, Kosuke, Nio, Kenta, Nakano, Michitaka, Arita, Shuji, hitoshi kusaba, Odashiro, Keita, Yoshinao Oda, Intraluminal superior vena cava metastasis from adenosquamous carcinoma of the duodenum: A case report, ONCOLOGY LETTERS, 10.3892/ol.2015.3938, 11, 1, 605-609, 2016.01.
371. Ohike N,, Suzuki R, Isobe T, Norose T, Shiokawa A,, Kunimura T,, Kenichi Kohashi, Yoshinao Oda, A Case of Pancreatic Undifferentiated Carcinoma Mimicking Proximal-Type Epithelioid Sarcoma., JOP. J Pancreas (Online), 17, 1, 75-80, 2016.01.
372. Kayo Tokumaru, Eikichi Ihara, Tsutomu Iwasa, Souichi Itaba, Yukishige Andou, Eiji Oki, Nobuyoshi Takizawa, Minako Hirahashi, Yoshinao Oda, Kazuhiko Nakamura, A case of A 3 - mm ileal neuroendocrine tumor with distant lymph node metastasis, GASTROENTEROLOGICAL ENDOSCOPY, 10.3390/en12030532, 58, 1, 10-14, 2016.01, A 53 - year - old man was referred to our hospital for evaluation and treatment of an ileal neuroendocrine tumor (NET). Colonoscopy revealed a xanthochromic submucosal tumor of 3 mm in diameter in the terminal ileum. It was diagnosed as NET by histological analysis of a biopsy specimen. Preoperative examinations including contrast - enhanced CT, FDG - PET and small - bowel endoscopy did not reveal synchronous or distant metastatic lesions. As a result, the patient was diagnosed as having clinical stage I (cT1, N0, M0) NET. The patient underwent segmental resection of the ileum with D3 lymph node dissection. Despite the small diameter of the tumor, the final pathological diagnosis was grade 2 ileal NET accompanied by metastasis to the ileocolic lymph nodes (#203). Surgical resection and appropriate lymph node dissection should thus be considered for the treatment of ileal NET, regardless of tumor size..
373. Kazuki Takada, Gouji Toyokawa, Tatsuro Okamoto, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Takatoshi Fujishita, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara, An immunohistochemical analysis of PD-L1 protein expression in surgically resected small cell lung cancer using different antibodies and criteria, Anticancer research, 36, 7, 3409-3412, 2016.01, Background: Programmed cell death ligand 1 (PD-L1) expression in lung cancer appears to be important in immunotherapy, as its expression can predict responses to programmed cell death-1 (PD-1)-blocking antibodies. However, a definitive antibody and cut-off value for PD-L1 expression are urgently needed. Materials and Methods: The PD-L1 expression in 40 surgically resected small cell lung cancer (SCLC) specimens was evaluated by immunohistochemistry (IHC) with three different antibodies: clones E1L3N, 28-8, and SP142, and using three different evaluations: the Allred score, 1% cut-off, and 5% cut-off. Results: The percentage of tumors with positive PD-L1 expression was inconsistent in the IHC evaluations using the Allred score and 1% cut-off. However, the IHC evaluations using the 5% cut-off showed similar rates of expression using the three different antibodies. Conclusion: The results of this study provided detailed evidence on the frequency of PD-L1 expression in surgically resected SCLC, which may be a useful reference for identifying patients with PD-L1-expressing SCLC..
374. Yoshihiko Inoue, Shiho Terawaki, Kazuko Imamura, Yumiko Kubota, Masazumi Tsuneyoshi, Kenichi Kohashi, Yuichi Yamada, Yoshinao Oda, Angiomatoid fibrous histiocytoma, Nishinihon Journal of Dermatology, 10.2336/nishinihonhifu.78.219, 78, 3, 219-220, 2016.01.
375. Kinuko Nagayoshi, Takashi Ueki, Tatsuya Manabe, Sho Endo, Shuntaro Nagai, Kosuke Yanai, Naoki Mochidome, Minako Hirahashi, Yoshinao Oda, Masafumi Nakamura, Five cases of laparoscopic bowel resection for intestinal endometriosis, Japanese Journal of Gastroenterological Surgery, 10.5833/jjgs.2015.0154, 49, 8, 762-771, 2016.01, We herein present our initial experience of laparoscopic bowel surgery in 5 patients with intestinal endometriosis. Three patients had ileal endometriosis and 2 had rectal endometriosis. Four of the 5 patients presented with intestinal obstruction, while 1 patient underwent emergency surgery for bowel perforation. All patients wished to conceive children in the future, and laparoscopic resection of the affected lesions was performed with preservation of the uterus and uterine appendages in all patients. The endometrial glands were found within the thickened bowel wall of the resected specimens in all patients. The patients' postoperative courses were uneventful, and none developed postoperative recurrence of intestinal endometriosis during the follow-up period. Laparoscopic surgery for intestinal endometriosis can be safely performed and may be useful as a minimally invasive surgery for young women..
376. Masaki Shiota, Naohiro Fujimoto, Kenjiro Imada, Akira Yokomizo, Momoe Itsumi, Ario Takeuchi, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito, Potential role for YB-1 in castration-resistant prostate cancer and resistance to enzalutamide through the androgen receptor V7, Journal of the National Cancer Institute, 10.1093/jnci/djw005, 108, 7, 2016.01, Background: Although androgen deprivation therapy for advanced prostate cancer initially exerts excellent anticancer effects, most prostate cancer treated with androgen deprivation therapy eventually recurs as castration-resistant prostate cancer (CRPC). Although aberrant kinase activation has been proposed as a mechanism of castration resistance, comprehensive kinase profiles in CRPC remain unknown. Therefore, we aimed to elucidate the kinome in CRPC as well as the role of key molecules. Methods: We utilized a kinome array in androgen-dependent LNCaP and castration-resistant CxR cells. The effect of Y-box binding protein-1 (YB-1) on androgen receptor (AR) expression was examined by quantitative polymerase chain reaction and western blot analysis. The association between polymorphisms in the YB-1 gene determined by genotyping and YB-1 expression evaluated by immunohistochemistry in prostate cancer tissues, as well as outcome in metastatic prostate cancer, were investigated by the Cochran-Armitage test and the Cox proportional hazards model, respectively. All statistical tests were two-sided. Results: One hundred fifty-six of 180 kinase phosphorylation sites, including ERK and RSK, were activated in CRPC cells, leading to increased phosphorylation of YB-1, which is a key molecule in the progression to CRPC. YB-1 signaling regulated AR V7 expression, and YB-1 inhibition augmented the anticancer effect of enzalutamide. Moreover, polymorphism (rs12030724) in the YB-1 gene affected YB-1 expression in 93 prostate cancer tissues (YB-1 positive rate; 14.3% in TT, 40.0% in AT, and 52.9% in AA, P = .04) and associated with probability of progression in 104 metastatic prostate cancer case patients (AT/TT vs AA, hazard ratio = 0.49, 95% confidence interval = 0.32 to 0.77, P = .001). Conclusions: YB-1 appears to be a promising target to inhibit the development of castration resistance, even at the AR variant-expressing stage. Polymorphism in the YB-1 gene may be a promising predictive biomarker in hormonal therapy..
377. Akira Maekawa, Yoshinao Oda, Roles of Histopathological Diagnosis in Multidisciplinary Therapy for Soft-Tissue Sarcoma, Gan to kagaku ryoho. Cancer & chemotherapy, 43, 1, 24-26, 2016.01, Soft-tissue sarcoma (STS) is very rare malignant tumor with many kinds of histological subtypes and variants, as well as being a newly emerging entity. Because of its rarity, general pathologists are not familiar with STS and have difficulty making an accurate histopathological diagnosis in such cases. As an accurate diagnosis is essential for the selection of appropriate therapy, the Japanese Society of Pathology offers a nationwide consultation system. Some clinical trials for molecular targeted therapy have been conducted based on pathological examination findings. Pathologists play various roles in the future of sarcoma therapy..
378. Nobuhiro Fujita, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Yasuhiro Ushijima, Yukihisa Takayama, Daisuke Okamoto, Koichiro Morita, Ken Shirabe, Kazuhiro Koto, Yuichiro Kubo, Yoshinao Oda, Hiroshi Honda, Significance of the signal intensity of gadoxetic acid-enhanced MR imaging for predicting the efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma, Magnetic Resonance in Medical Sciences, 10.2463/mrms.2015-0012, 15, 1, 111-120, 2016.01, Purpose: We attempted to clarify the relationship between the signal intensity (SI) in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging and the efficacy of hepatic arterial infusion chemotherapy (HAIC) in hepatocellular carcinomas (HCCs). Methods: We enrolled 14 patients with HCCs who underwent gadoxetic acid-enhanced MR imaging prior to HAIC using cisplatin and 5-fluorouracil. In the hepatobiliary phase, we calculated the SI of the HCCs and the background liver. In cases with multiple HCCs, we calculated the SI of the largest lesion. Patients were classified into high (n = 7) and low intensity (n = 7) groups based on the median value of the SI ratio (SI of the tumor/SI of the background liver). We analyzed progression-free survival using the Kaplan-Meier method and the log-rank test. In the 5 patients with a history of HCC surgery, we compared the expression of immunohistochemical organic anion-transporting polypeptide (OATP) 8 between the high and low intensity groups by chi-square test. Results: The SI ratios were 0.568 ± 0.093 (mean ± standard deviation) in the high intensity group and 0.251 ± 0.086 in the low intensity group. Compared to the group with low signal intensity, the group with high signal intensity demonstrated significantly lower serum levels of alpha fetoprotein (AFP) (P = 0.0350), significantly higher progression-free survival (P = 0.0108), better differentiation of tumor grade at histologic examination (P = 0.0253), and significantly higher OATP8 expression (P = 0.0253). Conclusion: Patients with HCCs of high SI ratio in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging can respond better to HAIC..
379. Nobuyoshi Takizawa, Yoshihiro Ohishi , Minako Hirahashi, Shunsuke Takahashi, Kazuhiko Nakamura, Masao Tanaka, Yoshihiko Maehara, Ryoichi Takayanagi, Yoshinao Oda, Molecular characteristics of colorectal neuroendocrine carcinoma: the similarities with adenocarcinoma rather than neuroendocrine tumor.
, Hum Pathol., 46, 12, 1890-1900, 2015.12.
380. Lee, Lingaku, Igarashi, Hisato, Fujimori, Nao, Hijioka, Masayuki, Kawabe, Ken, Yoshinao Oda, Jensen, Robert T, Tetsuhide Ito, Long-term outcomes and prognostic factors in 78 Japanese patients with advanced pancreatic neuroendocrine neoplasms: a single-center retrospective study, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 10.1093/jjco/hyv143, 45, 12, 1131-1138, 2015.12.
381. Okado, Yasuko, Aoki, Mikiko, Hamasaki, Makoto, Koga, Kaori, Sueta, Takayuki, Shiratsuchi, Hideki, Yoshinao Oda, Nakagawa, Takashi;, Nabeshima, Kazuki, Tumor budding and laminin5-gamma 2 in squamous cell carcinoma of the external auditory canal are associated with shorter survival, SPRINGERPLUS, 10.1186/s40064-015-1620-4, 4, 2015.12.
382. Masaki Shiota, Itsumi, Momoe, Takeuchi, Ario, Imada, Kenjiro, Akira Yokomizo, Kuruma, Hidetoshi, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Naito, Seiji, Crosstalk between epithelial-mesenchymal transition and castration resistance mediated by Twist1/AR signaling in prostate cancer, ENDOCRINE-RELATED CANCER, 10.1530/ERC-15-0225, 22, 6, 889-900, 2015.12.
383. 山下 奈真, Tokunaga, Eriko, Hiroyuki Kitao, Hitchins, Megan, Inoue, Yuka, Tanaka, Kimihiro, Hisamatsu, Yuichi, Taketani, Kenji, Akiyoshi, Sayuri, Okada, Satoko, Yoshinao Oda, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Epigenetic Inactivation of BRCA1 Through Promoter Hypermethylation and Its Clinical Importance in Triple-Negative Breast Cancer, CLINICAL BREAST CANCER, 10.1016/j.clbc.2015.06.009, 15, 6, 498-504, 2015.12.
384. Ito, Takamichi, Uchi Hiroshi, Yamada, Yuichi, Yoshinao Oda, Masutaka Furue, Onychopapilloma manifesting longitudinal melanonychia: A mimic of subungual malignancy, JOURNAL OF DERMATOLOGY, 10.1111/1346-8138.13097, 42, 12, 1199-1201, 2015.12.
385. Masaki Naka, Yoshihiro Ohishi et al., Tsunehisa Kaku, Sumiko Watanabe, Sadafumi Tamiya, Fumihiko Ookubo, Kiyoko Kato, Yoshinao Oda, Setsuo Sugishima, Identification of Intranuclear Inclusions is Useful for the Cytological Diagnosis of Ovarian Clear Cell Carcinoma, DIAGNOSTIC CYTOPATHOLOGY, 10.1002/dc.23322, 43, 11, 879-884, 2015.11.
386. Toshimitsu Nishijima, Hidetaka Yamamoto, Takafumi Nakano, Torahiko Nakashima, Kenichi Taguchi, Muneyuki Masuda, Jun-ichi Motoshita, Shizuo Komune, Yoshinao Oda, Dual gain of HER2 and EGFR gene copy numbers impacts the prognosis of carcinoma ex pleomorphic adenoma, HUMAN PATHOLOGY, 10.1016/j.humpath.2015.07.014, 46, 11, 1730-1743, 2015.11.
387. Hida, Tomoyuk, Matsumoto, Shinji, Hamasaki, Makoto, Kawahara, Kunimitsu, Tohru Tsujimura, Kenzo Hiroshima, Toshiaki Kamei, Kenichi Taguchi, Akinori Iwasaki, Yoshinao Oda, Hiroshi Honda, Nabeshima, Kazuki, Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue, CANCER SCIENCE, 10.1111/cas.12769, 106, 11, 1635-1641, 2015.11.
388. Date, Kenjiro, Ohtsuka Takao, Fujimoto, Takaaki, Gotoh, Yoshitaka, Nakashima, Yohei, Kimura, Hideyo, Matsunaga, Taketo, Mori, Yasuhisa, Mochidome Naoki, Miyazaki, Tetsuyuki, Yoshinao Oda, Masao Tanaka, Masafumi Nakamura, GNAS and KRAS mutational analyses of intraductal papillary neoplasms of the pancreas and bile duct developing in the same individual: A case report, PANCREATOLOGY, 10.1016/j.pan.2015.09.013, 15, 6, 713-716, 2015.11.
389. Inadomi, Kyoko, Kumagai, Hozumi, Takayoshi, Kotoe, Ariyama Hiroshi, hitoshi kusaba, Akihiro Nishie, Kohashi K, Yamamoto H, Kumagai R, Yamada Y, Hotokebuchi Y, Taguchi T, Iwa, Takase, Ken, Tanaka, Mamoru, Sagara, Kosuke, Okumura, Yuta, Nio, Kenta, Nakano, Michitaka, Arita, Shuji, Yoshinao Oda, Akashi, Koichi, Eishi Baba, Successful combination chemotherapy for metastatic inflammatory myofibroblastic tumor: A case report, Oncology Letters, 10.3892/ol.2015.3708, 10, 5, 2981-2985, 2015.11.
390. Hirofumi Bekki, Kenichi Kohashi, Akira Maekawa, Yuichi Yamada, Hidedaka Yamamoto, Katsumi Harimaya, Michiyuki Hakozaki, Kazuki Nabeshima, Yukihide Iwamoto, Yoshinao Oda, Elevated expression of HSP90 and the antitumor effect of an HSP90 inhibitor via inactivation of the Akt/mTOR pathway in undifferentiated pleomorphic sarcoma, BMC CANCER, 10.1186/s12885-015-1830-8, 15, 2015.10.
391. Hiroko Imamura, Yoshihiro Ohishi, Murasaki Aman, Kaai Shida, Tomoko Shinozaki, Nobuko Yasutake, Kenzo Sonoda, Kato K, Yoshinao Oda, Ovarian high-grade serous carcinoma with a noninvasive growth pattern simulating a serous borderline tumor.
, Hum Pathol. , 46, 10, 1455-1463, 2015.10.
392. Cases, Ana Ines, Ohtsuka Takao, HIdeyo Kimura, Zheng, Biao, Shindo, Koji, Yoshinao Oda, Mizumoto Kazuhiro, Masafumi Nakamura, Masao Tanaka, Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer, ONCOLOGY REPORTS, 10.3892/or.2015.4138, 34, 4, 1717-1725, 2015.10.
393. Ieiri, Satoshi, Kina Miyoshi, Nagata Takashi, Junko Miyata, Kenichi Kohashi, Yoshinao Oda, tomoaki taguchi, Current clinical features in diagnosis and treatment for immaturity of ganglia in Japan: analysis from 10-year nationwide survey, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-015-3774-0, 31, 10, 949-954, 2015.10.
394. Kimura, Hideyo, Ohtsuka Takao, Matsunaga, Taketo, Watanabe, Yusuke, Tamura, Koji, Ideno, Noboru, Aso, Teppei, Miyazaki, Tetsuyuki, Osoegawa, Takashi, Aishima, Shinichi, Yoshihiro Miysakaka, Junji Ueda, Hisato Igarashi, Yasuhiro Ushijima, Tetsuhide Ito, shunichi Tkahata, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Predictors and Diagnostic Strategies for Early-Stage Pancreatic Ductal Adenocarcinoma A Retrospective Study, PANCREAS, 10.1097/MPA.0000000000000393, 44, 7, 1148-1154, 2015.10.
395. Shunsuke Takahashi, Kenichi Kohashi, Hidetaka Yamamoto, Minako Hirahashi, Reiko Kumagai, Nobuyoshii Takizawa, Kazuhiko Nakamura, Yoshihiko Maehara, Masao Tanaka, Takayanagi, Ryoichi, Yoshinao Oda, Expression of adhesion molecules and epithelial-mesenchymal transition factors in medullary carcinoma of the colorectum, HUMAN PATHOLOGY, 10.1016/j.humpath.2015.05.023, 46, 9, 1257-1266, 2015.09.
396. Hisamatsu, Yuichi, Tokunaga, Eriko, Nami Yamashita, Akiyoshi, Sayuri, Okada, Satoko, Nakashima, Yuichiro, Taketani, Kenj, Aishima, Shinichi, Yoshinao Oda, Morita, Masaru, Yoshihiko Maehara, Impact of GATA-3 and FOXA1 expression in patients with hormone receptor-positive/HER2-negative breast cancer, BREAST CANCER, 10.1007/s12282-013-0515-x, 22, 5, 520-528, 2015.09.
397. Hatano, Mihoko, Yoshihiro Matsumoto, Jun-ichi Fukushi, Matsunobu, Tomoya, Endo, Makoto, Okada S, Iura, Kunio, Kamura, Satoshi, Fujiwara, Toshifumi, 飯田 圭一郎, Fujiwara, Yuko, Nabeshima, Akira, Yokoyama, Nobuhiko, Fukushima, Suguru, Yoshinao Oda, Iwamoto, Yukihide, Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone, CLINICAL & EXPERIMENTAL METASTASIS, 10.1007/s10585-015-9729-y, 32, 6, 579-591, 2015.08.
398. Yoshida, Rintaro, Morita, Masaru, Fumihiro Shoji, Nakashima, Yuichiro, Miura, Naoko, Yoshinaga, Keiji, Koga, Tadashi, Tokunaga, Eriko, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Yoshihiko Maehara, Clinical Significance of SIP1 and E-cadherin in Patients with Esophageal Squamous Cell Carcinoma, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-014-4314-1, 22, 8, 2608-2614, 2015.08.
399. Zheng, Biao, Ohuchida Kenoki, Cui, Lin, Zhao, Ming, Shindo, Koji, Fujiwara, Kenji, Manabe Tatsuya, Torata, Nobuhiro, Taiki Moriyama, Yoshihiro Miysakaka, Ohtsuka Takao, Takahata, Shunichi, Mizumoto Kazuhiro, Yoshinao Oda, Masao Tanaka, TM4SF1 as a prognostic marker of pancreatic ductal adenocarcinoma is involved in migration and invasion of cancer cells, INTERNATIONAL JOURNAL OF ONCOLOGY, 10.3892/ijo.2015.3022, 47, 2, 490-498, 2015.08.
400. Minami, Mariko, Shima, Takahiro, Kato Koji, Kohashi K, Yamamoto H, Kumagai R, Yamada Y, Hotokebuchi Y, Taguchi T, Iwa, Tsuchihashi, Kenji, Oku, Seido, Shimokawa, Tomonori, Tochigi, Taro, Goichi Yoshimoto, Kamezaki, Kenjiro, Takenaka, Katsuto, Iwasaki, Hiromi, Yoshinao Oda, Miyamoto, Toshihiro, Akashi, Koichi, Successful treatment of adult Langerhans cell histiocytosis with intensified chemotherapy, INTERNATIONAL JOURNAL OF HEMATOLOGY, 10.1007/s12185-015-1778-0, 102, 2, 244-248, 2015.08.
401. Takeshi Nakahara, Yamada, Yuichi, 伊藤 絵里子, Kido-Nakahara, Makiko, Yoshinao Oda, Kiryu, Hiromaro, Masutaka Furue, Case of ossifying epithelioid hemangioendothelioma on the forearm, JOURNAL OF DERMATOLOGY, 10.1111/1346-8138.12915, 42, 8, 841-842, 2015.08.
402. Bekki, Yuki, Kimura, Yasue, Morita, Masaru;, Zaitsu, Yoko, Hiroshi Saeki, Tatsuro Okamoto, Eiji Oki, Shingo Baba, Yoshinao Oda, Yoshihiko Maehara, Esophageal cancer associated with bilateral hilar lymphadenopathy caused by sarcoid-like reactions: a report of two cases, ESOPHAGUS, 10.1007/s10388-014-0454-4, 12, 3, 322-326, 2015.07.
403. Kuma Yuki, Ito Takamichi, Nagae K, Mizote Y, Nakahara T, Uchi Hiroshi, Yamada Y, Okura M, Yoshinao Oda, Yamashita T, Masutaka Furue, Two cases of cutaneous squamous cell carcinoma arising in immunosuppressed patients with chronic human papillomavirus infection., Case Rep Dermatol. , 7, 2, 178-182, 2015.07.
404. Takashima, Yoko, Kamitani Takeshi, Satoshi Kawanami, Nagao, Michinobu, Yonezawa, Masato, Yamasaki, Yuzo, Shingo Baba, Yabuuchi, Hidetake, Hida, Tomoyuki, Kenichi Kohashi, Nakamura, Katsuya, Hiromichi Sonoda, Yoshinao Oda, Hiroshi Honda, Mediastinal paraganglioma, JAPANESE JOURNAL OF RADIOLOGY, 10.1007/s11604-015-0436-z, 33, 7, 433-436, 2015.07.
405. Akira Maekawa, Kenichi Kohashi, Yuichi Yamada, Akira Nakamizo, Koji Yoshimoto, Masahiro Mizoguchi, Toru Iwaki, Yoshinao Oda, A case of intracranial solitary fibrous tumor/hemangiopericytoma with dedifferentiated component., Neuropathology, 10.1111/neup.12181, 35, 3, 260-265, 2015.06.
406. Iguchi, Tomohiro, Shirabe, Ken, Aishima, Shinichi, Wang, Huanlin, Nobuhiro Fujita, Ninomiya, Mizuki, Yamashita Yo-ichi, ikegami Toru, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshinao Oda, Yoshihiko Maehara, New Pathologic Stratification of Microvascular Invasion in Hepatocellular Carcinoma: Predicting Prognosis After Living-donor Liver Transplantation, TRANSPLANTATION, 10.1097/TP.0000000000000489, 99, 6, 1236-1242, 2015.06.
407. Akira Maekawa, Kenichi Kohashi, Yuichi Yamada, Akira Nakamizo, Koji Yoshimoto, Masahiro Mizoguchi,, Toru Iwaki, Yoshinao Oda, A case of intracranial solitary fibrous tumor/hemangiopericytoma with dedifferentiated component., Neuropathology, 10.1111/neup.12181, 35, 3, 260-265, 2015.06.
408. Tsuda M, Nakashima Y, Ikeda M, Shimada S, Nomura M, Matsushima T, Takahashi S, Aishima S, Yoshinao Oda, Aishima S, Takayanagi R, Intravascular Large B-Cell Lymphoma Complicated by Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis that was Successfully Treated with Rituximab-Containing Chemotherapy.
, J Clin Exp Hematop. , 55, 1, 39-43, 2015.06.
409. Konishi H, Ken Shirabe, Nakagawara H, Harimoto Norifumi, Yamashita Y, ikegami Toru, Tomoharu Yoshizumi, Yuji Soejima, Yoshinao Oda, Yoshihiko Maehara, Suppression of SIRT1 activity in noncancerous tissues of HCC: possible association with non-B non-C hepatitis pathogenesis, Cancer Sci, 10.1111/cas.12653, 106, 5, 542-549, 2015.05.
410. Minami M, Shima T, Kato K, Hidetaka Yamamoto, Tsuchihashi K, Oku S, Shimokawa T, Tochigi T, Goichi Yoshimoto, Kenjiro Kamezaki, Takenaka K, Iwasaki H, Yoshinao Oda, Miyamoto T, koichi akashi, Successful treatment of adult Langerhans cell histiocytosis with intensified chemotherapy., Int J Hematol, in press, 2015.05.
411. Konishi, Hideyuki, Shirabe, Ken, Nakagawara, Hidekazu, Harimoto Norifumi, Yamashita Yo-ichi, ikegami Toru, Tomoharu Yoshizumi, Yuji Soejima, Yoshinao Oda, Yoshihiko Maehara, Suppression of silent information regulator 1 activity in noncancerous tissues of hepatocellular carcinoma: Possible association with non-B non-C hepatitis pathogenesis, CANCER SCIENCE, 10.1111/cas.12653, 106, 5, 542-549, 2015.05.
412. Okano, Shinji, Takahara, Masakazu, Tanaka, Maya, Nakahara, Takeshi, Suzuki, Hanako, Fujii, Hiroshi, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Masutaka Furue, Cutaneous epithelioid angiomatous nodule in a patient with a history of multiple pyogenic granulomas, EUROPEAN JOURNAL OF DERMATOLOGY, 10.1684/ejd.2015.2527, 25, 3, 268-269, 2015.05.
413. Nakamura K, Honda K, Akahoshi K, Ihara E, Matsuzaka H, Sumida Y, Yoshimura D, Akiho H, Motomura Y, Iwasa T, Komori K, Chijiwa Y, Honda N, Ochiai T, Oya M, Yoshinao Oda, Ryoichi Takayanagi, Suitability of the expanded indication criteria for the treatment of early gastric cancer by endoscopic submucosal dissection: Japanese multi-center large-scale retrospective analysis of short-term and long-term outcomes., Scand J Gastroenterol, 50, 4, 413-422, 2015.04.
414. Yuki Tanaka, Eikichi Ihara, Shunsuke Takahashi, mayumi hirano, Kazuhiko Nakamura, Hirotada Akiho, Yoshinao Oda, Ryoichi Takayanagi, Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter, EUROPEAN JOURNAL OF PHARMACOLOGY, 10.1016/j.ejphar.2015.02.008, 752, 97-105, 2015.04.
415. Hajime Otsu, Eiji Oki, Ikawa-Yoshida Ayae, Hiroyuki Kawano, Ando Koji, Ida Satoshi, Yasue kimura, Shinichi Aishima, Hiroshi Saeki, Masaru Morita, Shunji Kohnoe, Yoshinao Oda, Yoshihiko Maehara, Correlation of HER2 Expression with Clinicopathological Characteristics and Prognosis in Resectable Gastric Cancer, ANTICANCER RESEARCH, 35, 4, 2441-2446, 2015.04.
416. Takashi Ueki, Nagayoshi K, Manabe Tatsuya, Maeyama Ryo, Akira Yokomizo, Hidetaka Yamamoto, Yoshinao Oda, Masao Tanaka, Laparoscopic en bloc excision of gastrointestinal stromal tumors of the rectum after neoadjuvant imatinib therapy: anteriorly extended intersphincteric resection combined with partial resection of the prostate, TECHNIQUES IN COLOPROCTOLOGY, 10.1007/s10151-014-1261-6, 19, 4, 247-251, 2015.04.
417. Kenta Nio, Shuji Arita, Taichi Isobe, hitoshi kusaba, Kenichi Kohashi, Tatsuhito Kijitani, Shingo Tamura, Gen Hirano, Kenji Mitsugi, Akitaka Makiyama, Taito Esaki, Ariyama Hiroshi, Yoshinao Oda, koichi akashi, Eishi Baba, Amrubicin monotherapy for patients with extrapulmonary neuroendocrine carcinoma after platinum-based chemotherapy, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 10.1007/s00280-015-2706-y, 75, 4, 829-835, 2015.04.
418. Harimoto Norifumi, ikegami Toru, Kazuki Takeishi, Yo-ichi Yamashita, Tomoharu Yoshizumi, Shinichi Aishima, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Education and imaging. Hepatology: Rare Stevens-Johnson syndrome and vanishing bile duct syndrome induced by acetaminophen, requiring liver transplantation., J Gastroenterol Hepatol., 30, 4, 2015.04.
419. Nakamura K, Akahoshi K, Honda K, Ihara E, Matsuzaka H, Sumida Y, Yoshimura D, Akiho H, Motomura Y, Tsutomu Iwasa, Komori K, Chijiwa Y, NAOHIKO HARADA5, TOSHIAKI OCHIAI6, MASAFUMI OYA, Yoshinao Oda, Ryoichi Takayanagi, Suitability of the expanded indication criteria for the treatment of early gastric cancer by endoscopic submucosal dissection: Japanese multi-center large-scale retrospective analysis of short-term and long-term outcomes., Scand J Gastroenterol, 50, 4, 413-422, 2015.04.
420. Otsu, Hajime, Eiji Oki, Ikawa-Yoshida, Ayae;, Kawano, Hiroyuki, Ando, Koji, Ida, Satoshi, Kimura, Yasue, Aishima, Shinichi, Hiroshi Saeki, Morita, Masaru, Kohnoe, Shunji, Yoshinao Oda, Yoshihiko Maehara, Correlation of HER2 Expression with Clinicopathological Characteristics and Prognosis in Resectable Gastric Cancer, ANTICANCER RESEARCH, 35, 4, 2441-2446, 2015.04.
421. YoshimasaTanaka, Eikichi Ihara, Katsuya Hirano, ShunsukeTakahashi, Mayumi Hirano, Kazuhiko Nakamura, Hirotada Akiho, Yoshinao Oda, Ryoichi Takayanagi, Trypsin-inducedbiphasicregulationoftoneintheporcinelower
esophagealsphincter, Eur J Pharmacol, 752, 97-105, 2015.04.
422. Harimoto Norifumi, ikegami Toru, Kazuki Takeishi,, Yamashita Y, Tomoharu Yoshizumi, Shinichi Aishima, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Education and imaging. Hepatology: Rare Stevens-Johnson syndrome and vanishing bile duct syndrome induced by acetaminophen, requiring liver transplantation., J Gastroenterol Hepatol., 30, 4, 2015.04.
423. Nagae, Konosuke, 内 博史, Ito, Takamichi, Moroi, Yoichi, 小田 義直, 古江 増隆, Osteomalacia induced by a phosphaturic mesenchymal tumor secreting fibroblast growth factor 23, EUROPEAN JOURNAL OF DERMATOLOGY, 10.1684/ejd.2014.2503, 25, 2, 199-200, 2015.04.
424. Nio, Kenta, Arita, Shuji, Isobe, Taichi, hitoshi kusaba, Kenichi Kohashi, Kajitani, Tatsuhiro, Tamura, Shingo, Tamura, Shingo, Hirano, Gen, Mitsugi, Kenji, Makiyama, Akitaka, Esaki, Taito, Ariyama Hiroshi, Yoshinao Oda, Akashi, Koichi, Eishi Baba, Amrubicin monotherapy for patients with extrapulmonary neuroendocrine carcinoma after platinum-based chemotherapy, CANCER CHEMOTHERAPY AND PHARMACOLOGY, 10.1007/s00280-015-2706-y, 75, 4, 829-835, 2015.04.
425. Ueki, T, Nagayoshi, K, Manabe Tatsuya, Maeyama, R, Akira Yokomizo, Yamamoto H, Yoshinao Oda, Masao Tanaka, Laparoscopic en bloc excision of gastrointestinal stromal tumors of the rectum after neoadjuvant imatinib therapy: anteriorly extended intersphincteric resection combined with partial resection of the prostate, TECHNIQUES IN COLOPROCTOLOGY, 10.1007/s10151-014-1261-6, 19, 4, 247-251, 2015.04.
426. Yoko Zaitsu, Eiji Oki, Ando Koji, Ida Satoshi, Yasue kimura, Hiroshi Saeki, Masaru Morita, Minako Hirahashi, Yoshinao Oda, Yoshihiko Maehara, Loss of Heterozygosity of PTEN (Encoding Phosphate and Tensin Homolog) Associated with Elevated HER2 Expression Is an Adverse Prognostic Indicator in Gastric Cancer, ONCOLOGY, 10.1159/000368984, 88, 3, 189-194, 2015.03.
427. Takamichi Ito, Yumiko Kaku, Nagae Konosuke, Nakano Misa, Takeshi Nakahara, Yoshinao Oda, Akihito Hagihara, Masutaka Furue, Uchi Hiroshi, Tumor thickness as a prognostic factor in extramammary Paget's disease, JOURNAL OF DERMATOLOGY, 10.1111/1346-8138.12764, 42, 3, 269-275, 2015.03.
428. Noboru Ideno, Ohtsuka Takao, Taketo Matsunaga, Hideyo Kimura, Yusuke Watanabe, Koji Tamura, Teppei Aso, Shinichi Aishima, Yoshihiro Miyasaka, JUNJI UEDA, Ohuchida Kenoki, Shunichi Takahata, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Clinical Significance of GNAS Mutation in Intraductal Papillary Mucinous Neoplasm of the Pancreas With Concomitant Pancreatic Ductal Adenocarcinoma, PANCREAS, 44, 2, 311-320, 2015.03.
429. Reiko Kumagai, Kenichi Kohashi, Shunsuke Takahashi, Hidetaka Yamamoto, Minako Hirahashi, Kenichi Taguchi, Kenichi Nishiyama, Yoshinao Oda, Mucinous phenotype and CD10 expression of primary adenocarcinoma of the small intestine: Possible association with biological behavior, genetic alteration and microsatellite instability status., World J Gastroenterol. , 21, 9, 2700-2710, 2015.03.
430. Nagae Konosuke, Takamichi Ito, Yoichi Moroi, Yoshinao Oda, Masutaka Furue, Osteomalacia induced by a phosphaturic mesenchymal tumor secreting fibroblast growth factor 23., European Journal of Dermatology, in press, 2015.03.
431. Yusuke Mizuuchi, Shinichi Aishima, Ohuchida Kenoki, Koji Shindo, Minoru Fujino, Masami Hattori, Tetsuyuki Miyazaki, Mizumoto Kazuhiro, Masao Tanaka, Yoshinao Oda, Anterior gradient 2 downregulation is mediated by epithelial mesenchymal transition and correlates with poor outcome in pancreatic ductal adenocarcinoma., Lab Invest. , 95, 2, 193-206, 2015.02.
432. Kenichi Kohashi, Yuichi Yamada, Yuka Hotokebuchi, Hidetaka Yamamoto, tomoaki taguchi, Yukihide Iwamoto, Yoshinao Oda, ERG and SALL4 expressions in SMARCB1/INI1-deficient tumors: a useful tool for distinguishing epithelioid sarcoma from malignant rhabdoid tumor, HUMAN PATHOLOGY, 10.1016/j.humpath.2014.10.010, 46, 2, 225-230, 2015.02.
433. YOSHIAKI KINOSHITA, Sakura Tanaka, Ryota Souzaki, Kina Miyoshi, Kenichi Kohashi, Yoshinao Oda, Tesuya Nakatsura, tomoaki taguchi, Glypican 3 Expression in Pediatric Malignant Solid Tumors, EUROPEAN JOURNAL OF PEDIATRIC SURGERY, 10.1055/s-0034-1393961, 25, 1, 138-144, 2015.02.
434. Yuichi Yamada, Kenichi Kohashi, Hirofumi Bekki, Takeaki Ishi, Kunio Iura, Akira Maekawa, Hidetaka Yamamoto, Yukihide Iwamoto, Yoshinao Oda, Malignant solitary fibrous tumor with high-grade nuclear atypia: An alternate entity for the undetermined tumor group, PATHOLOGY RESEARCH AND PRACTICE, 10.1016/j.prp.2014.12.002, 211, 2, 117-124, 2015.02.
435. Nabeshima A, Matsumoto Y, Fukushi J, Tomoya Matsunobu, Makoto Endo, Fujiwara T, Ken-ichiro Iida, Fujiwara Y, Hatano M, Yokoyma N, Fukushima S, Yoshinao Oda, Yukihide Iwamoto, Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways, BRITISH JOURNAL OF CANCER, 10.1038/bjc.2014.637, 112, 3, 547-555, 2015.02.
436. Kuniko Nagayoshi, Takashi Ueki, Kosuke Tashiro, Yusuke Mizuuchi, Manabe Tatsuya, Hiromitsu Araki, Yoshinao Oda, Satoru Kuhara, Masao Tanaka, Galanin plays an important role in cancer invasiveness and is associated with poor prognosis in stage II colorectal cancer, ONCOLOGY REPORTS, 10.3892/or.2014.3660, 33, 2, 539-546, 2015.02.
437. Koji Tamura, Ohtsuka Takao, Taketo Matsunaga, Hideyo Kimura, Watanabe Yusuke, Noboru Ideno, Teppei Aso, Tetsuyuki Miyazaki, Ohuchida Kenoki, Shunichi Takahata, Tetsuhide Ito, Yasuhiro Ushijima, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis, SURGERY, 10.1016/j.surg.2014.09.013, 157, 2, 277-284, 2015.02.
438. Koji Tamura, Ohtsuka Takao, Taketo Matsunaga, Hideyo Kimura, Watanabe Yusuke, Noboru Ideno, Teppei Aso, Tetsuyuki Miyazaki, Ohuchida Kenoki, Shunichi Takahata, Tetsuhide Ito, Yasuhiro Ushijima, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis, SURGERY, 10.1016/j.surg.2014.09.013, 157, 2, 277-284, 2015.02.
439. Yuichiroh Umemoto, Shinji Okano, Yoshihiro Matsumoto, Hidekazu Nakagawara, Rumi Matono, Shohei Yoshiya, Yo-ichi Yamashita, Tomoharu Yoshizumi, ikegami Toru, Yuji Soejima, Mamoru Harada, Shinichi Aishima, Yoshinao Oda, Ken Shirabe, Yoshihiko Maehara, Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy, JOURNAL OF GASTROENTEROLOGY, 10.1007/s00535-014-0933-3, 50, 1, 65-75, 2015.01.
440. Yuichiroh Umemoto, Shinji Okano, Yoshihiro Matsumoto, Hidekazu Nakagawara, Rumi Matono, Shohei Yoshiya, Yo-ichi Yamashita, Tomoharu Yoshizumi, ikegami Toru, Yuji Soejima, Mamoru Harada, Shinichi Aishima, Yoshinao Oda, Ken Shirabe, Yoshihiko Maehara, Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy, JOURNAL OF GASTROENTEROLOGY, 10.1007/s00535-014-0933-3, 50, 1, 65-75, 2015.01.
441. Nakano T, Toshimitsu Nishijima, Tamiya S, Shiratsuchi H, Nakashima T, Shizuo Komune, Yoshinao Oda, Hyalinizing clear cell carcinoma with EWSR1-ATF1 fusion gene; report of 3 cases with molecular analyses., VIRCHOWS ARCHIV, 466, 1, 37-43, 2015.01.
442. Kohei Nakata, Ohuchida Kenoki, Mizumoto Kazuhiro, Shinichi Aishima, Yoshinao Oda, Eishi Nagai, Masao Tanaka, Micro RNA-373 is Down-regulated in Pancreatic Cancer and Inhibits Cancer Cell Invasion, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-014-3676-8, 21, 564-574, 2014.12.
443. Ohtsuka Takao, Taketo Matsunaga, Hideyo Kimura, Yusuke Watanabe, Koji Tamura, Noboru Ideno, Teppei Aso, Yoshihiro Miyasaka, JUNJI UEDA, Shunichi Takahata, Takashi Osoegawa, Hisato Igarashi, Tetsuhide Ito, Yasuhiro Ushijima, Fumihiko Ookubo, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Role of Pancreatic Juice Cytology in the Preoperative Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas in the Era of International Consensus Guidelines 2012, WORLD JOURNAL OF SURGERY, 10.1007/s00268-014-2684-y, 38, 11, 2994-3001, 2014.11.
444. Teppei Aso, Ohtsuka Takao, Taketo Matsunaga, Hideyo Kimura, Yusuke Watanabe, Koji Tamujra, Noboru Ideno, Takashi Osoegawa, Shunichi Takahata, Koji Shindo, Yasuhiro Ushijima, Shinichi Aishima, Yoshinao Oda, Tetsuhide Ito, Mizumoto Kazuhiro, Masao Tanaka, "High-Risk Stigmata" of the 2012 International Consensus Guidelines Correlate With the Malignant Grade of Branch Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas, PANCREAS, 43, 8, 1239-1243, 2014.11.
445. Kubo S, Kinoshita M, Takemura S, Tanaka S, Shinkawa H, Nishioka T, Hamano G, Ito T, Abue M, Aoki M, Nakagawa K, Unno M, Hijioka S, Fujiyoshi T, Shimizu Y, Muzuguchi T, Ken Shirabe, Akihiro Nishie, Yoshinao Oda, Takenaka K, Characteristics of printing company workers newly diagnosed with occupational chola ngiocarcinoma., J Hepatobiliary Pancreat Sci. , 21, 11, 809-817, 2014.11.
446. Shinichi Aishima, Yuki Tanaka, Yuichiro Kubo, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda, Bile duct adenoma and von Meyenburg complex-like duct arising in hepatitis and cirrhosis: Pathogenesis and histological characteristics, PATHOLOGY INTERNATIONAL, 10.1111/pin.12209, 64, 11, 551-559, 2014.11.
447. Takanobu Takanobu, Yuichro Nakashima, Ando Koji, Keiji Yoshinaga, Hiroshi Saeki, Eiji Oki, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara, Nuclear Expression of Chemokine Receptor CXCR4 Indicates Poorer Prognosis in Gastric Cancer, ANTICANCER RESEARCH, 34, 11, 6397-6403, 2014.11.
448. Iguchi Tomohiro, Ken Shirabe, Shinichi Aishima, Huanlin Wang, Fujita Nobuhiro, Mizuki Ninomiya, Yo-ichi Yamashita, ikegami Toru, Hideaki Uchiyama, Tomoharu Yoshizumi, Yoshinao Oda, Yoshihiko Maehara, New Pathologic Stratification of Microvascular Invasion in Hepatocellular Carcinoma: Predicting Prognosis After Living-Donor Liver Transplantation., Transplantation, 2014.11.
449. Takamichi Ito, Maiko Wada, Yuki Kuma, Makiko Kido-Nakahara, Yuichi Yamada, Shinji Okano, Yoshinao Oda, Masutaka Furue, Pigmented Bowen's disease with prominent amyloid deposition on the eyelid, INDIAN JOURNAL OF DERMATOLOGY VENEREOLOGY & LEPROLOGY, 10.4103/0378-6323.144204, 80, 6, 558-560, 2014.11.
450. Ohtsuka Takao, Tamura, Koji, Ideno, Noboru, Aso Teppei, Nagayoshi Yosuke, Kono Hiroshi, JUNJI UEDA, Shunichi Takahata, Aso Akira, Hisato Igarashi, Tetsuhide Ito, Yasuhiro Ushijima, Ookubo Fumihiko, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, The role of ERCP in the era of EUS-FNA for preoperative cytological confirmation of resectable pancreatic ductal adenocarcinoma, SURGERY TODAY, 10.1007/s00595-014-0845-0, 44, 10, 1887-1892, 2014.10.
451. Yasunori Oda, Shinichi Aishima, Katsuya Morimatsu, Koji Shindo, Minoru Fujino, Yusuke Mizuuchi, Masami Hattori, Testuyuki Miyazaki, Masao Tanaka, Yoshinao Oda, Pancreatic intraepithelial neoplasia in the background of invasive ductal carcinoma of the pancreas as a prognostic factor, HISTOPATHOLOGY, 10.1111/his.12397, 65, 3, 389-387, 2014.09.
452. Kina Miyoshi, Kenichi Kohashi, Fumiuyoshi Fushimi, Hidetaka Yamamoto, Junji Kishimoto, tomoaki taguchi, Yukihide Iwamoto, Yoshinao Oda, Close correlation between CXCR4 and VEGF expression and frequent CXCR7 expression in rhabdomyosarcoma, HUMAN PATHOLOGY, 10.1016/j.humpath.2014.05.012, 45, 9, 1900-1909, 2014.09.
453. Kenji Fujikawa, Ohuchida Kenoki, Masafumi Sada, Kohei Horioka, Ulrich, Charles D., III, Koji Shindo, Ohtsuka Takao, Shunichi Takahata, Mizumoto Kazuhiro, Yoshinao Oda, Masao Tanaka, CD166/ALCAM Expression Is Characteristic of Tumorigenicity and Invasive and Migratory Activities of Pancreatic Cancer Cells, PLOS ONE, 10.1371/journal.pone.0107247, 9, 9, 2014.09.
454. Akio Sakamoto, Yusuke Takahashi, Yoshinao Oda, Yukihide Iwamoto, Aggressive clinical course of epithelioid angiosarcoma in the femur: a case report, WORLD JOURNAL OF SURGICAL ONCOLOGY, 10.1186/1477-7819-12-281, 12, 1, 2014.09.
455. Yuichiro Kubo, Shinichi Aishima, Yuki Tanaka, Koji Shindo, Yusuke Mizuuchi, Koichiro Abe, Ken Shirabe, Yoshihiko Maehara, Hiroshi Honda, Yoshinao Oda, Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma, HUMAN PATHOLOGY, 10.1016/j.humpath.2014.03.008, 45, 8, 1610-1617, 2014.08.
456. Yuichiro Kubo, Shinichi Aishima, Yuki Tanaka, Koji Shindo, Yusuke Mizuuchi, Koichiro Abe, Ken Shirabe, Yoshihiko Maehara, Hiroshi Honda, Yoshinao Oda, Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma, HUMAN PATHOLOGY, 10.1016/j.humpath.2014.03.008, 45, 8, 1610-1617, 2014.08.
457. Kitaoka K, Tanaka K, Mizusawa J, Kimura A, Hiraga H, Kawai A, Tomoya Matsunobu, Matsumine A, Araki N, Yoshinao Oda, Fukuda H, Yukihide Iwamoto, A Randomized Phase II/III Trial of Perioperative Chemotherapy with Adriamycin Plus Ifosfamide Versus Gemcitabine Plus Docetaxel for High-grade Soft Tissue Sarcoma: Japan Clinical Oncology Group Study JCOG1306, Jpn J Clin Oncol, 44, 8, 765-769, 2014.08.
458. Tagushi T, Kobayashi H, Kanamori Y, Segawa O, Yamataka A, Sugiyama M, Iwanaka T, Shimojima N, Kuroda T, Nakagawa A, Yoshinao Oda, Kina Miyoshi, Satoshi Ieiri, Isolated intestinal neuronal dysplasia Type B (IND-B) in Japan: results from a nationwide survey, PEDIATRIC SURGERY INTERNATIONAL, 10.1007/s00383-014-3542-6, 30, 8, 815-22, 2014.08.
459. Keisuke Ikeda, Eiji Oki, Hiroshi Saeki, Ando Koji, Masaru Morita, Yoshinao Oda, Masakazu Imamura, Yoshihiro Kakeji, Yoshihiko Maehara, Intratumoral Lymphangiogenesis and Prognostic Significance of VEGFC Expression in Gastric Cancer, ANTICANCER RESEARCH, 34, 8, 3911-3915, 2014.08.
460. Yasue kimura, Eiji Oki, Ayae Yoshida, Shinichi Aishima, Yoko Zaitsu, Hajime Ohtsu, Ando Koji, Ida Satoshi, Hiroshi Saeki, Masaru Morita, Tetsuya Kusumoto, Yoshinao Oda, Yoshihiko Maehara, Significance of Accurate Human Epidermal Growth Factor Receptor-2 (HER2) Evaluation as a New Biomarker in Gastric Cancer, ANTICANCER RESEARCH, 34, 8, 4207-4212, 2014.08.
461. Hokazono K, Ueki T, Nagayoshi K, Hatae t, Yutaka Koga, Minako Hirahashi, Yoshinao Oda, Masao Tanaka, A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps, Oncol Letters , 8, 1937-1944, 2014.08.
462. Tajima S, Kenichi Kohashi, Fan B, Doi W, Kimura R, Tamura Y, Abe H, Yoshinao Oda, Aggressive Angiomyxoma of the Pelvis with a Cellular Nodule Composed of Tumor Cells showing Epithelioid Features., Rare Tumors. , 6, 3, 2014.08.
463. Shin Akagawa, Ohuchida Kenoki, Nobuhiro Torata, Masami Hattori, Daiki Eguchi, Kenji Fujiwara, Shingo Kozono, Lin Cui, Naoki Ikenaga, Ohtsuka Takao, Shinichi Aishima, Mizumoto Kazuhiro, Yoshinao Oda, Masao Tanaka, Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer.
, Int J Oncol. Int J Oncol. 2014 Jul;45(1):113-20. , 10.3892/ijo.2014.2391., 45, 1, 113-120, 2014.07.
464. Akagawa, Shin, Ohuchida Kenoki, Torata, Nobuhiro, Hattori Masami, Eguchi Daiki, Fujiwara, Kenji, Kozono, Shingo, Cui, Lin, Ikenaga, Naoki, Ohtsuka Takao, Shinichi Aishima, Mizumoto Kazuhiro, Yoshinao Oda, Masao Tanaka, Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer, INTERNATIONAL JOURNAL OF ONCOLOGY, 10.3892/ijo.2014.2391, 45, 1, 113-120, 2014.07.
465. Yohei Mano, Shinichi Aishima, Yuichiro Kubo, Yuki Tanaka, Motomura T, Toshima T, Ken Shirabe, Abe K, Yoshihiko Maehara, Yoshinao Oda, Correlation between Biological Marker Expression and Fluorine-18 Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma Measured by Positron Emission Tomography., Am J Clin Pathol., 42, 3, 391-397, 2014.07.
466. Koji Shindo, Shinichi Aishima, Ohuchida Kenoki, Minoru Fujino, Yusuke Mizuuchi, Masami Hattori, Ohtsuka Takao, Mizumoto Kazuhiro, Masao Tanaka, Yoshinao Oda, Podplanin expression in the cystic wall correlate with the development of intraductal papillary mucinous neoplasm., Virchows Arch , 465, 265-273, 2014.07.
467. Tsukamoto Y, Watanabe T, Nishimoto S, Kakibuchi m, Yuichi Yamada, Kenichi Kohashi, Yoshinao Oda, Hirota S, STAT6-positive intraorbital papillary tumor: A rare variant of solitary fibrous tumor?, Pathol Res Pract. , 10.1016/j.prp.2014.03.001, 210, 7, 450-453, 2014.07.
468. Kumagai H, Nio K, Okumura Y, Komoda M, Shirakawa T, Kusaba H, Yasuda S, Odashiro K, Arita S, Ariyama H, Yuichi Yamada, Hidetaka Yamamoto, Yoshinao Oda, Nakamura K, koichi akashi, Eishi Baba, Successful Chemoradiotherapy for Undifferentiated Malignant Neoplasm Arising from the Left Pulmonary Artery., Case Rep Oncol , 7, 2, 484-490, 2014.07.
469. Mikako Osada, Shinichi Aishima, Minako Hirahashi, Nobuyoshi Takizawa, Shunsuke Takahashi, Kazuhiko Nakamura, Masao Tanaka, Yoshihiko Maehara, Ryoichi Takayanagi, Yoshinao Oda, Combination of hepatocellular markers is useful for the prediction of prognosis in gastric hepatoid adenocarcinoma., Hum Pathol. 2014 Jun;45(6):1243-50. (corresponding) , 10.1016/j.humpath.2014.02.003. , 45, 6, 1243-1250, 2014.06.
470. Yosuke Nagayoshi, Masafumi Nakamura, Kazuhiro Matsuoka, Ohtsuka Takao, Yasuhisa Mori, Hiroshi Kono, Teppei Aso, Noboru Ideno, Shunichi Takahata, Ryo Akihide, Hiroyuki Takeda, Tetsuhide Ito, Yoshinao Oda, Yaeta Endo, Tatsuya Sawasaki, Masao Tanaka, Profiling of Autoantibodies in Sera of Pancreatic Cancer Patients., Ann Surg Oncol, in press , 10.1245/s10434-014-3574-0, 3, supplement, 459-465, 2014.06.
471. Shohei Yoshiya, Yukiko Fujimoto, Yuki Bekki, Hideyuki Konishi, Yo-ichi Yamashita, ikegami Toru, Tomoharu Yoshizumi, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Impact of EGF single-nucleotide polymorphism on recurrence of hepatocellular carcinoma after hepatectomy in patients with chronic HCV infection., Cancer Sci. 2014 Apr 7, in press , 10.1111/cas.12415., 105, 6, 646-650, 2014.06.
472. Fujita Nobuhiro, Akihiro Nishie, Shinichi Aishima, Yuichiro Kubo, Asayama Yoshiki, Kousei Ishigami, Daisuke Kakihara, Yasuhiro Ushijima, Yukihisa Takayama, Ken Shirabe, Yoshinao Oda, Hiroshi Honda, Role of tumor-associated macrophages in the angiogenesis of well-differentiated hepatocellular carcinoma: Pathological-radiological correlation., Oncol Rep. 2014 Apr 16, in press , 10.3892/or.2014.3138, 31, 6, 2499-2505, 2014.06.
473. Hiroyuki Kawano, Hiroshi Saeki, Hiroyuki Kitao, Yasuo Tsuda, Hajime Otsu, Koji Ando, Ito Shuhei, Akinori Egashira, Eiji Oki, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara, Chromosomal instability associated with DNA global hypomethylation relates to initiation and progression of esophageal squamous cell carcinoma. , Annals of Surgical Oncology, in press , 2014.06.
474. Nagayoshi, Yosuke, Aso, Teppei, Ohtsuka Takao, Kono Hiroshi, Ideno Noboru, Hisato Igarashi, Shunichi Takahata, Yoshinao Oda, Tetsuhide Ito, Masao Tanaka, Peroral pancreatoscopy using the SpyGlass system for the assessment of intraductal papillary mucinous neoplasm of the pancreas, JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES, 10.1002/jhbp.44, 21, 6, 410-417, 2014.06.
475. Tsutsumi, Kosuke, Ohtsuka Takao, Fujino, Minoru, Nakashima, Hiroshi, Shinichi Aishima, JUNJI UEDA, Shunichi Takahata, Masafumi Nakamura, Yoshinao Oda, Masao Tanaka, Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification, JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES, 10.1002/jhbp.47, 21, 6, 418-425, 2014.06.
476. Mikako Osada, Shinichi Aishima, 平橋 美奈子, Nobuyoshi Takizawa, Shunsuke Takahashi, Kazuhiko Nakamura, Masao Tanaka, Yoshihiko Maehara, Ryoichi Takayanagi, Yoshinao Oda, Combination of hepatocellular markers is useful for the prediction of prognosis in gastric hepatoid adenocarcinoma., Hum Pathol. , 10.1016/j.humpath.2014.02.003. , 45, 6, 1243-1250, 2014.06.
477. Yosuke Nagayoshi, Masafumi Nakamura, Kazuhito Matsuoka, Ohtsuka Takao, Yasuhisa Mori, Hiroshi Kono, Teppei Aso, Noboru Ideno, Shunichi Takahata, Akihide Ryo, Hiroyuki Takeda, Tetsuhide Ito, Yoshinao Oda, Yaeta Endo, Testuya Sawasaki, Masao Tanaka, Profiling of Autoantibodies in Sera of Pancreatic Cancer Patients, ANNALS OF SURGICAL ONCOLOGY, 10.1245/s10434-014-3574-0, 21, 459, 465, 2014.06.
478. Harimoto Norifumi, ikegami Toru, H Nakagawara, Y Yamashita, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, T Ikeda, Ken Shirabe, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara, Chronic immune-mediated reaction syndrome as the cause of late graft mortality in living donor liver transplantation for primary biliary cirrhosis., Transplant Proc. , 46, 5, 1438-1443, 2014.06.
479. Shohei Yoshiya, Yukiko Fujimoto, Yuki Bekki, Hideyuki Konishi, Yo-ichi Yamashita, ikegami Toru, Tomoharu Yoshizumi, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Impact of EGF single-nucleotide polymorphism on recurrence of hepatocellular carcinoma after hepatectomy in patients with chronic HCV infection., Cancer Sci. 2014 Apr 7, in press , 10.1111/cas.12415., 105, 6, 646-650, 2014.06.
480. Fujita Nobuhiro, Akihiro Nishie, Shinichi Aishima, Yuichiro Kobo, Asayama Yoshiki, Kousei Ishigami, Daisuke Kakihara, Yasuhiro Ushijima, Yukihisa Takayama, Ken Shirabe, Yoshinao Oda, Hiroshi Honda, Role of tumor-associated macrophages in the angiogenesis of well-differentiated hepatocellular carcinoma: Pathological-radiological correlation, ONCOLOGY REPORTS, 10.3892/or.2014.3138, 31, 6, 2499-2505, 2014.06.
481. Hiroyuki Kawano, Hiroshi Saeki, Hiroyuki Kitao, Yasuo Tsuda, Hajime Otsu, Ando Koji, Ito Shuhei, Akinori Egashira, Eiji Oki, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara, Chromosomal instability associated with DNA global hypomethylation relates to initiation and progression of esophageal squamous cell carcinoma. , Annals of Surgical Oncology , 21, Suppl 4, 696-702, 2014.06.
482. Harimoto Norifumi, ikegami Toru, Hidekazu Nakagawara, Yo-ichi Yamashita, Tomoharu Yoshizumi, Hideaki Uchiyama, Yuji Soejima, Ken Shirabe, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara, Chronic immune-mediated reaction syndrome as the cause of late graft mortality in living-donor liver transplantation for primary biliary cirrhosis., Transplant Proc, 10.1016/j.transproceed.2014.02.021., 46, 5, 1438-1443, 2014.06.
483. Yusuke Takahashi, Kenichi Kohashi, Yuichi Yamada, Makoto Endo, Nokitaka Setsu, Takeaki Ishii, Hidetaka Yamamoto, Yukihide Iwamoto, Yoshinao Oda, Activation of the Akt/mammalian target of rapamycin pathway in myxofibrosarcomas
, Hum Pathol. 2014 May;45(5):984-93. (corresponding) , 10.1016/j.humpath.2013.12.012. , 45, 5, 984-993, 2014.05.
484. Shojiro Matsushita, Hideya Onishi, Kenji Nakano, Iori Nagamatsu, Akira Imaizumi, Masami Hattori, Yoshinao Oda, Masao Tanaka, Mitsuo Katano, The Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer., Cancer Sci 105(3): 272-80, 2014 , 10.1111/cas.12354., 105, 3, 272-280, 2014.05.
485. Takahashi Yusuke, Kenichi Kohashi, Yamada Yuichi, Makoto Endo, Setsu, Nokitaka, Ishii Takeaki, Hidetaka Yamamoto, Yukihide Iwamoto, Yoshinao Oda, Activation of the Akt/mammalian target of rapamycin pathway in myxofibrosarcomas, HUMAN PATHOLOGY, 10.1016/j.humpath.2013.12.012, 45, 5, 984-993, 2014.05.
486. Shojiro Matsushita, Hideya Onishi, Kenji Nakano, Iori Nagamatsu, Akira Imaizumi, Masami Hattori, Yoshinao Oda, Masao Tanaka, Mitsuo Katano, The Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer., Cancer Sci , 10.1111/cas.12354., 105, 3, 272-280, 2014.05.
487. Shohei Yoshiya, ikegami Toru, Tomoharu Yoshizumi, Wang Huanlin, Noboru Harada, Yo-ichi Yamashita, Akihiro Nishie, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Fairly rare de novo inflammatory pseudotumor in a graft after living donor liver transplantation, LIVER TRANSPLANTATION, 10.1002/lt.23828, 20, 5, 616-618, 2014.05.
488. Takamichi Ito, Eriko Itoh, Ayami Koda-Maeda, Hironao Kiryu, Yuichi Yamada, Toshiharu Yamashita, Yoshinao Oda, Hidemasa Furue, Lipoblastomatosis on the sole showing spontaneous regression, EUROPEAN JOURNAL OF DERMATOLOGY, 10.1684/ejd.2014.2333, 24, 3, 399-401, 2014.05.
489. Yuske Inatomi, Takamichi Ito, Nagae Konosuke, Yamada Yuichi, Mari Kiyomatsu, Nakano Misa, Uchi Hiroshi, Yoshinao Oda, Hidemasa Furue, Hybrid perineurioma-neurofibroma in a patient with neurofibromatosis type 1, clinically mimicking malignant peripheral nerve sheath tumor, EUROPEAN JOURNAL OF DERMATOLOGY, 10.1684/ejd.2014.2353, 24, 3, 412-413, 2014.05.
490. N Kubo, M Morita, Y Nakashima, H Kitao, Akinori Egashira, Hiroshi Saeki, Eiji Oki, Yoshihiro Kakeji, Yoshinao Oda, Yoshihiko Maehara, Oxidative DNA damage in human esophageal cancer: Clinicopathological analysis of 8-hydrodeoxyguanosine and its repair enzyme.

, Dis Esophagus. Apr;27(3):285-93, 2014 , 10.1111/dote.12107, 27, 3, 285-293, 2014.04.
491. Minako Hirahashi, Yutaka Koga, Reiko Kumagai, Shinichi Aishima, Kenichi Taguchi, Yoshinao Oda, Induced nitric oxide synthetase and peroxiredoxin expression in intramucosal poorly differentiated gastric cancer of young patients., Pathol Int. 2014 Apr;64(4):155-63. , 10.1111/pin.12152., 64, 4, 155-63, 2014.04.
492. Teppei Aso, Ohtsuka Takao, Koji Tamura, Noboru Ideno, Hiroshi Kono, Yosuke Nagayoshi, Ohuchida Kenoki, JUNJI UEDA, Shunichi Takahata, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Elevated Expression Level of MicroRNA-196a Is Predictive of Intestinal-Type Intraductal Papillary Mucinous Neoplasm of the Pancreas, Pancreas 43(3) April: 361-366, 2014 , 10.1097/MPA.0000000000000042., 43, 3, 361-366, 2014.04.
493. Kinuko Nagayoshi, Takashi Ueki, Yasunobu Nishioka, Manabe Tatsuya, Yusuke Mizuuchi, Minako Hirahashi, Yoshinao Oda, Masao Tanaka, Tumor deposit is a poor prognostic indicator for patients who have stage II and III colorectal cancer with fewer than 4 lymph node metastases but not for those with 4 or more., Dis Colon Rectum 57(4) April: 467-474, 2014. , 10.1097/DCR.0000000000000059., 57, 5, 467-474, 2014.04.
494. Kohei Nakata, Ohuchida Kenoki, Mizumoto Kazuhiro, Shinichi Aishima, Yoshinao Oda, Eishi Nagai, Masao Tanaka, Micro RNA-373 is Down-regulated in Pancreatic Cancer and Inhibits Cancer Cell Invasion., Ann Surg Oncol. 2014 Apr 19. , 2014.04.
495. Kubo N, Morita M, Nakashima Y, Hiroyuki Kitao, Egashira A, Hiroshi Saeki, Eiji Oki, Kakeji Y, Yoshinao Oda, Yoshihiko Maehara, Oxidative DNA damage in human esophageal cancer: Clinicopathological analysis of 8-hydrodeoxyguanosine and its repair enzyme.

, Dis Esophagus. , 10.1111/dote.12107, 27, 3, 285-293, 2014.04.
496. Minako Hirahashi, Yutaka Koga, Reiko Kumagai, Shinichi Aishima, Kenichi Taguchi, Yoshinao Oda, Induced nitric oxide synthetase and peroxiredoxin expression in intramucosal poorly differentiated gastric cancer of young patients, PATHOLOGY INTERNATIONAL, 10.1111/pin.12152, 64, 4, 155-163, 2014.04.
497. Teppei Aso, Ohtsuka Takao, Koji Tamura, Noboru Ideno, Hiroshi Kono, Yosuke Nagayoshi, Ohuchida Kenoki, JUNJI UEDA, Shunichi Takahata, Koji Shindo, Shinichi Aishima, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Elevated Expression Level of MicroRNA-196a Is Predictive of Intestinal-Type Intraductal Papillary Mucinous Neoplasm of the Pancreas, PANCREAS, 10.1097/MPA.0000000000000042, 43, 3, 361-366, 2014.04.
498. Kinuko Nagayoshi, Takashi Ueki, Yasunobu Nishioka, Manabe Tatsuya, Yusuke Mizuuchi, Minako Hirahashi, Yoshinao Oda, Masao Tanaka, Tumor Deposit Is a Poor Prognostic Indicator for Patients Who Have Stage II and III Colorectal Cancer With Fewer Than 4 Lymph Node Metastases but not for Those With 4 or More, DISEASES OF THE COLON & RECTUM, 10.1097/DCR.0000000000000059, 57, 4, 467-474, 2014.04.
499. Yasunari Sakai, Ryota Souzaki, Hidetaka Yamamoto, Yuki Matsushita, Hazumu Nagata, Ishizaki Yoshito, Hiroyuki Torisu, Yoshinao Oda, tomoaki taguchi, Shaw Chad A, Toshiro Hara, Testicular sex cord-stromal tumor in a boy with 2q37 deletion syndrome, BMC MEDICAL GENOMICS, 10.1186/1755-8794-7-19, 7, 1, 2014.04.
500. Yasunari Sakai, Ryota Souzaki, Hidetaka Yamamoto, Yuki Matsushita, Hazumu Nagata, Ishizaki Yoshito, Hiroyuki Torisu, Yoshinao Oda, tomoaki taguchi, Shaw Chad A, Toshiro Hara, Testicular sex cord-stromal tumor in a boy with 2q37 deletion syndrome, BMC MEDICAL GENOMICS, 10.1186/1755-8794-7-19, 7, 1, 2014.04.
501. Yuka Hotokebuchi, Kenichi Kohashi, Satoshi Toyoshima, Naoko Matsumoto, Toshinori Nakashima, Yoshinao Oda, Congenital peribronchial myofibroblastic tumor, PATHOLOGY INTERNATIONAL, 10.1111/pin.12141, 64, 4, 189-191, 2014.04.
502. Yuichi Yamada, Kenichi Kohashi, Fumiyoshi Fushimi, Yusuke Takahashi, Nokitaka Setsu, Makoto Endo, Hidetaka Yamamoto, Shoji Tokunaga, Yukihide Iwamoto, Yoshinao Oda, Activation of Akt-mTOR pathway and receptor tyrosin kinase in solitary fibrous tumors., Cancer Mar 15 120(6): 864-76, 2014 (corresponding), 10.1002/cncr.28506., 120, 6, 864-876, 2014.03.
503. Hidetaka Yamamoto, Katsumi Atakaki, Katsuya Morimatsu, Yoko Zaitsu, Aya Fujita, Kenichi Kohashi, Minako Hirahashi, Junichi Motoshita, Yumi Oshiro, Yoshinao Oda, Insulin-like growth factor II mRNA-binding protein-3 (IMP3) expression in gastrointestinal mesenchymal tumors.

, Hum Pathol 45(3): 481-7, 2014. , 10.1016/j.humpath.2013.10.010, 45, 3, 481-487, 2014.03.
504. Akira Aso, Eikichi Ihara, Takashi Osoegawa, Kazuhiko Nakamura, Soichi Itaba, Hisato Igarashi, Tetsuhide Ito, Shinichi Aishima, Yoshinao Oda, Masao Tanaka, Ryoichi Takayanagi, Key endoscopic ultrasound features of pancreatic ductal adenocarcinoma smaller than 20mm
, Scand J Gastroenterol. 2014 Mar;49(3):332-8. , 10.3109/00365521.2013.878745., 49, 3, 332-338, 2014.03.
505. Hidetaka Yamamoto, Arakaki K, Katsuya Morimatsu, Yoko Zaitsu, Aya Fujita, Kenichi Kohashi, 平橋 美奈子, Junichi Motoshita, Yumi Oshiro, Yoshinao Oda, Insulin-like growth factor II mRNA-binding protein-3 (IMP3) expression in gastrointestinal mesenchymal tumors.

, Hum Pathol , 10.1016/j.humpath.2013.10.010, 45, 3, 481-487, 2014.03.
506. Yuichi Yamada, Kenichi Kohashi, Fumiyoshi Fushimi, Yusuke Takahashi, Nokitaka Setsu, Makoto Endo, Hidetaka Yamamoto, Shoji Tokunaga, Yukihide Iwamoto, Yoshinao Oda, Activation of Akt-mTOR pathway and receptor tyrosin kinase in solitary fibrous tumors., Cancer , 10.1002/cncr.28506., 120, 6, 864-876, 2014.03.
507. Akira Aso, Eikichi Ihara, Takashi Osoegawa, Kazuhiko Nakamura, Soichi Itaba,, Hisato Igarashi, Tetsuhide Ito, Shinichi Aishima, Yoshinao Oda, Masao Tanaka, Ryoichi Takayanagi, Key endoscopic ultrasound features of pancreatic ductal adenocarcinoma smaller than 20mm
, Scand J Gastroenterol. , 10.3109/00365521.2013.878745., 49, 3, 332-338, 2014.03.
508. Kimura H, Ohtsuka Takao, Hiroki Toma, JUNJI UEDA, Yusuke Mizuuchi, Hidetaka Yamamoto, Shunichi Takahata, Yoshinao Oda, Takashi Ueki, Masao Tanaka, A Case of Gastrointestinal Stromal Tumor of the Jejunum Successfully Treated by Preoperative Induction Chemotherapy with Imatinib Mesylate Administered through Jejunostomy and Subsequent Surgical Resection., Gan To Kagaku Ryoho, 41, 3, 391-394, 2014.03.
509. K Tamura, Ohtsuka Takao, N Ideno, T Aso, Kouji Shindo, Shinichi Aishima, Ohuchida Kenoki, Shunichi Takahata, T Ito, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Treatment strategy for main duct intraductal papillary mucinous neoplasms of the pancreas based on the assessment of recurrence in the remnant pancreas after resection: a retrospective review.
, Ann Surg. 2014 Feb;259(2):360-8. , 10.1097/SLA.0b013e3182a690ff., 259, 9, 360-368, 2014.02.
510. Tamura K, Ohtsuka Takao, Ideno N, Aso T, Shindo K, Shinichi Aishima, Ohuchida Kenoki, Shunichi Takahata, Yasuhiro Ushijima, Tetsuhide Ito, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Treatment Strategy for Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas Based on the Assessment of Recurrence in the Remnant Pancreas After Resection A Retrospective Review, ANNALS OF SURGERY, 10.1097/SLA.0b013e3182a690ff, 259, 2, 360-368, 2014.02.
511. Iori Nagamatsu, Hideya Onishi, Shojiro Matsushita, Makoto Kubo, Masaya Kai, Akira Imaizumi, Kenji Nakano, Masami Hattori, Yoshinao Oda, Masao Tanaka, Mitsuo Katano, Notch4 is a potential therapeutic target for triple negative breast cancer.

, Anticancer Res. 2014 Jan;34(1):69-80. , 34, 1, 69-80, 2014.01.
512. Yasuhisa Mori, Ohtsuka Takao, Koji Tamura, Noboru Ideno, Teppei Aso, Hiroshi Kono, Yosuke Nagayoshi, JUNJI UEDA, Shunichi Takahata, Shinichi Aishima, Fumihiko Ookubo, Yoshinao Oda, Masao Tanaka, Intraoperative irrigation cytology of the remnant pancreas to detect remnant distinct pancreatic ductal adenocarcinoma in patients with intraductal papillary mucinous neoplasm undergoing partial pancreatectomy., Surgery. 2014 Jan;155(1):67-73. , doi: 10.1016/j.surg.2013.06.059., 155, 1, 67-73, 2014.01.
513. Kosuke Tsutsumi, Ohtsuka Takao, Minoru Fijino, Hiroshi Nakashima, Shinichi Aishima, JUNJI UEDA, Shunichi Takahata, Masafumi Nakamura, Yoshinao Oda, Masao Tanaka, Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification.
, J Hepatobiliary Pancreat Sci. 2014 Jun;21(6):418-25 , doi: 10.1002/jhbp.47, 21, 6, 418-425, 2014.01.
514. Yosuke Nagayoshi, Teppei Aso, Ohtsuka Takao, Hiroshi Kono, Noboru Ideno, Hisato Igarashi, Shunichi Takahata, Yoshinao Oda, Tetsuhide Ito, Masao Tanaka, Peroral pancreatoscopy using the SpyGlass system for the assessment of intraductal papillary mucinous neoplasm of the pancreas., J Hepatobiliary Pancreat Sci, 2014 Jun;21(6):410-7 , doi: 10.1002/jhbp.44, 21, 6, 410-417, 2014.01.
515. Nobuhiro Torata, Ohuchida Kenoki, Shin Akagawa, LIN CUI, Shingo Kozono, Mizumoto Kazuhiro, Shinichi Aishima, Yoshinao Oda, Masao Tanaka, Tissue tablet method: an efficient tissue banking procedure applicable to both molecular analysis and frozen tissue microarray.

, Hum Pathol. 2014 Jan;45(1):143-52. , 10.1016/j.humpath.2013.08.013., 45, 1, 143-152, 2014.01.
516. Cases Ana Ines, Ohtsuka Takao, Minoru Fujino, Noboru Ideno, Shingo Kozono, Zhao Ming, Ohuchida Kenoki, Shinichi Aishima, Masatoshi Nomura, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Expression of glucagon-like peptide 1 receptor and its effects on biologic behavior in pancreatic neuroendocrine tumors.
, Pancreas. 2014 Jan;43(1):1-6. , 10.1097/MPA.0b013e3182a71537, 43, 1, 1-6, 2014.01.
517. Yoh Dobashi, Eiichi Saro, Yoshinao Oda, Johji Inazawa, Akaishi Ooi, Significance of Akt activation and AKT gene increases in bone bone and soft tissue tumors., Hum Pathol. 2014 Jan;45(1):127-36., 10.1016/j.humpath.2013.06.024., 45, 1, 127-136, 2014.01.
518. Yoo Hyun Song, M Shiota, Akira Yokomizo, Takeshi Uchiumi, Kiyoshima Keijiro, Kentaro Kuroiwa, Yoshinao Oda, Seiji Naito, Twist1 and Y-box-binding protein-1 are potential prognostic factors in bladder cancer.
, Urol Oncol.2014 Jan;32(1):31.el-7 , 32, 1, 2014.01.
519. Kenichi Kohashi, Hidetaka Yamamoto, Reiko Kumagai, Yuichi Yamada, Yuka Hotokebuchi, tomoaki taguchi, Yukihide Iwamoto, Yoshinao Oda, Differential microRNA expression profiles between malignant rhabdoid tumor and epithelioid sarcoma: miR193a-5p is suggested to downregulate SMARCB1 mRNA expression., 10.1038/modpathol.2013.213. , 27, 6, 832-839, 2014.01.
520. Dobashi Y, Sato E, Yoshinao Oda, Inazawa J, Ooi A, Significance of Akt activation and AKT gene increases in soft tissue tumors., Hum Pathol, 10.1016/j.humpath.2013.06.024., 45, 1, 127-136, 2014.01.
521. Cases, Ana Ines, Ohtsuka Takao, Fujino Monoru, Ideno, Noboru, Kozono, Shingo, Zhao, Ming, Ohuchida Kenoki, Shinichi Aishima, Masatoshi Nomura, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, Expression of Glucagon-Like Peptide 1 Receptor and its Effects on Biologic Behavior in Pancreatic Neuroendocrine Tumors, PANCREAS, 10.1097/MPA.0b013e3182a71537, 43, 1, 1-6, 2014.01.
522. Torata N, Ohuchida Kenoki, Akagawa S, Cui L, Kozono S, Mizumoto Kazuhiro, Shinichi Aishima, Yoshinao Oda, Masao Tanaka, Tissue tablet method: an efficient tissue banking procedure applicable to both molecular analysis and frozen tissue microarray., Hum Pathol. 2014 Jan;45(1):143-52., 10.1016/j.humpath.2013.08.013., 45, 1, 143-152, 2014.01.
523. Mori, Yasuhisa, Ohtsuka Takao, Tamura, Koji, Ideno, Noboru, Aso, Teppei, Kono, Hiroshi, Nagayoshi, Yosuke, JUNJI UEDA, Shunichi Takahata, Shinichi Aishima, Ookubo Fumihiko, Yoshinao Oda, Masao Tanaka, Intraoperative irrigation cytology of the remnant pancreas to detect remnant distinct pancreatic ductal adenocarcinoma in patients with intraductal papillary mucinous neoplasm undergoing partial pancreatectomy, SURGERY, 10.1016/j.surg.2013.06.059, 155, 1, 67-73, 2014.01.
524. Nagamatsu, Iori, Hideya Onishi, Matsushita, Shojiro, Kubo Makoto, Kai Masaya, Imaizumi, Akira, Kenji Nakano, Hattori Masami, Yoshinao Oda, Masao Tanaka, Mitsuo Katano, NOTCH4 Is a Potential Therapeutic Target for Triple-negative Breast Cancer, ANTICANCER RESEARCH, 34, 1, 69-80, 2014.01.
525. Janette Mareska Rumbajan, Toshiyuki Maeda, Ryota Souzaki, Kazumasa Mitsui, Ken Higashimoto, Kazuhiko Nakabayashi, Hitomi Yatsuki, Kenichi Nishioka, Ryoko Harada, Shigehisa Aoki, Kenichi Kohashi, Yoshinao Oda, Kenichiro Hata, Tsutomu Saji, tomoaki taguchi, Hidenobu Soejima, Keiichiro Joh, Comprehensive analyses of imprinted differentially methylated regions revealed epigenetic and genetic characteristics of hepatoblastoma.

, BMC Cancer 2013 Dec 27;13(1):608. , 10.1186/1471-2407-13-608., 13, 1, 608, 2013.12.
526. Koji Shindo, Shinichi Aishima, Ohuchida Kenoki, Kenji Fujiwara, Minoru Fujino, Yusuke Mizuuchi, Masami Hattori, Mizumoto Kazuhiro, Masao Tanaka, Yoshinao Oda, Podoplanin expression in fibroblasts enhances the tumor progression of invasive ductal carcinoma of pancreas
, Mol Cancer 2013 Dec 20;12(1):168. (corresponding) , 10.1186/1476-4598-12-168., 12, 1, 168, 2013.12.
527. Ryota Souzaki, Satoshi Ieiri, Munenori Uemura, Ohuchida Kenoki, MORIMASA TOMIKAWA, YOSHIAKI KINOSHITA, Yuhki Koga, Aiko Suminoe, Kenichi Kohashi, Yoshinao Oda, Toshiro Hara, Makoto Hashizume, tomoaki taguchi, An augmented reality navigation system for pediatric oncologic surgery based on preoperative CT and MRI images.
, J Pediatr Surg. 2013 Dec;48(12):2479-83. , 10.1016/j.jpedsurg.2013.08.025., 48, 12, 2479-2483, 2013.12.
528. Yuichiro Nakashima, Keiji Yoshinaga, Hiroyuki Kitao, Koji Ando, Yasue kimura, Hiroshi Saeki, Eiji Oki, Masaru Morita, Yoshihiro Kakeji, Minako Hirahashi, Yoshinao Oda, Yoshihiko Maehara, Podoplanin is expressed at the invasive front of esophageal squamous cell carcinomas and is involved in collective cell invasion


, Cancer Sci 2013 Dec;104(12):1718-1725. , 10.1111/cas.12286, 104, 12, 1718-1725, 2013.12.
529. Eriko Kitao Tokunaga, Yuichi Hisamatsu, Kenji Taketani, Nami Yamashita, Akiyoshi Sayuri, Satoko Okada, Kimihito Tanaka, Hiroshi Saeki, Eiji Oki, Shinichi Aishima, Yoshinao Oda, Masaru Morita, Yoshihiko Maehara, Differential impact of the expression of the androgen receptor by age in estrogen receptor-positive breast cancer., Cancer Med. 2013 Dec;2(6):763-73. , 10.1002/cam4.138., 2, 6, 763-73, 2013.12.
530. Y Mano, Shinichi Aishima, Takasuke Fukuhara, Ken Shirabe, Yuichiro Kubo, Yuki Tanaka, Yoshihiko Maehara, Yoshinao Oda, Decreased Roundabout 1 expression promotes the development of intrahepatic cholangiocarcinoma.
, Hum Pathol 44(11):2419-2426,2013(corresponding) , 10.1016, 44, 11, 2419-2426, 2013.11.
531. Fumiyoshi Fushimi, Kenichi Taguchi, Hiroto Izumi, Kimitoshi Kohno, Michihiko Kuwano, MAYUMI ONO, Yutaka Nakashima, Tetsuro Takesue, Seiji Naito, Yoshinao Oda, Peroxiredoxins, thioredoxin and Y-box-binding pritein-1 expression in renal cell carcinoma arising in patients on dialysis., Virchow Archiv 463: Oct 553-562, 2013 (corresponding) , 10.1007/s00428-013-1460-y, 463, 553-562, 2013.10.
532. kenjiro Imada, Masaki Shiota, Kenichi Kohashi, Kentaro Kuroiwa, Yoo Hyun Song, Masaaki Sugimoto, Seiji Naito, Yoshinao Oda, Mutual regulation between Raf/MEK/ERK signaling and Y-box binding protein-1 promotes prostate cancer progression., Clin Cancer Res 19(17): 4638-4650, 2013 (corresponding), 10.1158/1078-0432.CCR-12-3705, 19, 17, 4638-4650, 2013.09.
533. Shimoji S, Koji Kato, Katsuto Takenaka, Hiromi IWASAKI, Toshihiro Miyamoto, Yoshinao Oda, koichi akashi, Takanori Teshima, Evaluating the association between histological manifestationsof cord colitis syndrome with GVHD., Bone Marroe Transplantation Sep 48, 1249-1252, 2013., 10.1038/bmt.2013.44, 48, 1249-1252, 2013.09.
534. K Morimatsu, Shinichi Aishima, Hidetaka Yamamoto, Yasunori Oda, Koji Shindo, Monoru Fujino, Masao Tanaka, Yoshinao Oda, Insulin-like growth factor II mRNA-binding protein-3 (IMP-3) is a valuable diagnosis and prognostic marker of intraductal papillary-mucinous neoplasm.
, Hum Pathol Sep;44(9):1714-1721,2013, 44, 9, 1714-1721, 2013.09.
535. Yasunori Oda, Shinichi Aishima, Koji Shindo, Minoru Fujino, Masao Tanaka, Yoshinao Oda, Different ezurin expression and phosphorylation of ezurin in PanIN, IPMN and invasive ductal carcinoma of pancreas.
, Hum Pathol 2013 Aug;44(8):1487-98(corresponding) , 44, 8, 1487-1498, 2013.08.
536. Naoki Yamanaka, Eishi Nagai, Ohuchida Kenoki, JUNJI UEDA, Hiroki Toma, Shuji Shimizu, Yoshinao Oda, Masao Tanaka, Feasibility of laparoscopic gastrectomy for advanced gastric cancer with positive peritoneal cytology., Surg Today. Aug;43(8):859-64, 2013 , 10.1007/s00595-012-0338-y, 43, 8, 859-864, 2013.08.
537. Hidetaka Yamamoto, Taro Tobo, Handa Mizuki, Setsu Nokitaka, Fijita Kohei, Oshiro Yumi, Mihara Yumi, Yasuji Yoshikawa, Yoshinao Oda, Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract after recognition of gastrointestinal stromal tumor., Histopathology Aug;63(2):194-207, 2013, 10.1111/his.12159., 63, 2, 194-207, 2013.08.
538. Setsu Nokitaka, Kenichi Kohashi, Fushimi Fumiyoshi, Makoto Endo, Hidetaka Yamamoto, Takahashi Yusuke, Yamada Yuichi, Ishii Takeaki, Yokoyama Koichiro, Yukihide Iwamoto, Yoshinao Oda, Prognostic impact of the activation status of Akt/mTOR pathway in synovial sarcoma., Cancer Oct 1;119(19):3504-3513, 2013 (corresponding), 10.1002/cncr.28255, 119, 19, 3504-3513, 2013.08.
539. T Nakano, Toshiharu Ninomiya, Mitsuho Onimaru, Kazuhiko Tsuruya, Yoshinao Oda, Takanari Kitazono, Yutaka Kiyohara, Chronic kidney disease is associated with neovascularization and intraplaque hemorrhage in coronary atherosclerosis in autopsy samples from Japanese elders: the Hisayama Study.
, Kidney Int Aug;84(2):373-380,2013, 84, 2, 373-380, 2013.08.
540. Moriyasu Yamauchi, Takafumi Nakano, Torahiko Nakashima, Ryuji Yasumatsu, Kazuki Hashimoto, Satoshi Toh, Hideki Shiratsuchi, Yoshinao Oda, Shizuo Komune, Interferon inducible IFI16 expression was not altered in Human Papillomavirus related Squamous Cell Carcinoma of the Oropharynx., ISRN OtolaryngologyVolume 2013 (2013), Article ID 263271, 7 pageshttp://dx.doi.org/10.1155/2013/263271, 10.1155/2013/263271, 2013.07.
541. Takafumi Nakano, Hidetaka Yamamoto, Sadafumi Tamiya, Hideki Shiratsuchi, Torahiko Nakashima, Nishiyama Ken-ichi, Shizuo Komune, Yoshinao Oda, HER2 and EGFR gene copy number alterations are present in high-grade salivary mucoepidermoid carcinoma irrespective of MAML2 fusion status.
, Histopathology Sep;63(3):378-392,2013(corresponding) , 63, 7, 378-392, 2013.07.
542. H Yamaguchi, Shinichi Aishima, Yoshinao Oda, Mizukami Hiroki, Tajiri Takuma, Yamada Sohsuke, Tasaki Takashi, Yamakita Keisuke, Imai Koji, Kawakami Fumi, Hara Shigeo, Hanada Keiji, Iiboshi Tomohiro, Fukuda Toshikatsu, Imai Hiroshi, Inoue Hiroyuki, Nagakawa Tatsuya, Muraoka Shunji, Furukawa Toru, M Shimizu, Distinctive histopathological findings of pancreatic hamartomas suggesting their “hamartomatous” nature: A study of 9 cases.
, Am J Surg Pathol 37(7):1006-1013,2013 July, 37, 7, 1006-1013, 2013.07.
543. Tadahisa Takeuchi, Yoshihiro Ohishi, Hiroko Imamura, Murasaki Aman, Kaai Shida, Hiroaki Kobayashi, Kiyoko Kato, Yoshinao Oda, Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma.
, Am J Surg Pathol. July;37(7):1091-1099,2013 , 37, 7, 1091-1099, 2013.06.
544. Shinichi Aishima, Yohei Mano, Yuki Tanaka, Yuichiro Kubo, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda, Different roles of inducible nitric oxide synthase and coclooxygenase-2 in carcinogenesis and metastasis of intrahepatic cholangiocarcinoma.
, Hum Pathol June;44(6):1031-1037,2013 , 44, 6, 1031-1037, 2013.06.
545. M Nagata, Yoshinao Oda, Takanari Kitazono, Yutaka Kiyohara, Secular trends in sudden unexpected death in a general population: the Hisayama study.
, American Heart Journal, in press , 2013.05.
546. Y Toomine, Yoshihiro Ohishi, Yoshinao Oda, Tsunehisa Kaku, Endometrial metaplasia: correlation of histological and cytological specimens obtained from 103 cases undergoing hysterectomy for endometrial carcinoma.
, Cytopathology. 2013 Mar 20, in press. doi: 10.1111/cyt.12055 , 2013.05.
547. Akio Sakamoto, Yoshinao Oda, Yukihide Iwamoto, Intraosseous ganglia: a series of 17 treated cases., Biomed Res Int. 2013;2013:462730. doi: 10.1155/2013/462730., 10.1155/2013/462730., 2013.04.
548. Hidetaka Yamamoto, Kenichi Kohashi, Aya Fujita, Yoshinao Oda, Fascin-1 overexpression and miR-133b down-regulation in the progression of gastrointestinal stromal tumor.
, Mod Pathol Apr;26(4):563-71, 2013, 2013.04.
549. Kenichi Kohashi, Tetsuya Nakatsura, YOSHIAKI KINOSHITA, Hidetaka Yamamoto, Yuichi Yamada, Tatsuro Tajiri, tomoaki taguchi, Yukihide Iwamoto, Yoshinao Oda, Glypican 3 expression in tumors with loss of SMARCB1/INI1 protein expression., Hum Pathol 44(4):526-533, 2013(corresponding), 10.1016/j.humpath.2012.06.014. , 44, 4, 526-533, 2013.04.
550. K Iida, Jun-ichi Fukushi, Yoshihiro Matsumoto, Yoshinao Oda, Yusuke Takahashi, T Fujiwara, Y Fujiwara-Okada, M Hatano, A Nabeshima, S Kamura, Yukihide Iwamoto, miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor.
, Cancer Cell Int. Mar 4;13(1):21, 2013 , 13, 1, 2013.03.
551. Y Fujiwara-Okada, Yoshihiro Matsumoto, Jun-ichi Fukushi, S Kamura, T Fujiwara, K Iida, M Hatano, Yoshinao Oda, Suguru Matsuura, HISAKATA YAMADA, Mayumi Ono, Yukihide Iwamoto, Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.
, Br J Cancer. 2013 Mar 5;108(4):836-47. , 2013.03.
552. H Iwasaki, K Nakano, K Shinkai, Y Kinukawa, Minako Hirahashi, Yoshinao Oda, Hideya Onishi, Mitsuo Katano, Hedgehog Gli3 activator signal augments tumorigenicity of colorectal cancer via upregulation of adherence-related genes.
, Cancer Sci Mar;104(3):328-336, 2013 , 2013.03.
553. Y Mano, Shinichi Aishima, N Fujita, T Motomura, akinobu taketomi, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda, Tumor-associated macrophage promotes tumor progression via STAT3 signaling in hepatocellular carcinoma., Pathobiology 80: 146-154, 2013 (corresponding) , 2013.02.
554. Suguru Matsuura, Takeshi Ishii, Makoto Endo, Yuusuke Takahashi, Nokitaka Setsu, Hidetaka Yamamoto, Sadafumi Tamiya, Yukihide Iwamoto, Yoshinao Oda, Epithelial and cartilaginous differentiation in clear cell chondrosarcoma.
, Hum Pathol 44(2) Feb : 237-243, 2013 (corresponding), 2013.02.
555. Masaharu Nagata, Toshiharu Ninomiya, Doi Yasufumi, Jun Hata, Fumie Ikeda, Naoko Mukai, Kazuhiko Tsuruya, Yoshinao Oda, Takanari Kitazono, Yutaka Kiyohara, Temporal trends in sudden unexpected death in a general population:
The Hisayama Study.
, Am Heart J. 2013 Jun;165(6):932-938., 10.1016/j.ahj.2013.02.028, 165, 6, 932-938, 2013.01.
556. Setsu Nokitaka, Kenichi Kohashi, Makoto Endo, Hidetaka Yamamoto, Sadafumi Tamiya, Yuusuke Takahashi, Yuichi Yamada, Shuichi Matsuda, Yukihide Iwamoto, Yoshinao Oda, Phosphorylation of signal transducer and activator of transcription 3 in soft tissue leiomyosarcoma is associated with a better prognosis.
, Int J Cancer 132(1):109-115, 2013 (corresponding), 132, 1, 109-115, 2013.01.
557. Taro Tobo, Minako Hirahashi, Takashi Yao, Shinichi Aishima, Yoshinao Oda, Ezrin expression and its phosphorylation in gastric carcinoma with lymphoid stroma and Epstein-Barr virus infection.
, Molecular and Clinical Oncology 1 (Jan): 220-224, 2013 , 2013.01.
558. L Zhu, Shinji Okano, Masakazu Takahara, Yoshinao Oda, Masutaka Furue, Expression of S100 protein family members in normal skin and sweat gland tumours., J Dermaltol Sci Jun:70(3):211-219,2013 , 10.1016, 70, 3, 211-219, 2013.01.
559. Toshihiko Nakamura, Takashi Yao, Yoshihiro Kakeji, H Anai, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara, Depressed type of intramucosal differentiated-type gastric cancer has high cell proliferation and reduced apoptosis compared with the elevated type.
, Gastric Cancer Jan;16(1): 94-99, 2013 (6th/ 7 authors), 2013.01.
560. Makoto Endo, Hidetaka Yamamoto, Nokitaka Setsu, Kenichi Kohashi, Yusuke Takahashi, Takeshi Ishii, M Hakozaki, M Aoki, Hirioshi Iwasaki, Yoh Dobashi, Kenichi Nishiyama, K Iida, Yoshihiro Matsumoto, Yukihide Iwamoto, Yoshinao Oda, Prognostic significance of AKT/mTOR and MAPK pathways and antitumor effect of mTOR inhibitor in NF1-related and sporadic malignant peripheral nerve sheath tumors.

, Clin Cancer Res Jan 15;19(2):450-461, 2013 (Corresponding) , 10.1158/1078-0432.CCR-12-1067, 19, 2, 450-461, 2013.01.
561. YOSHIAKI KINOSHITA, A Suminoe, H Inada, M Yagi, F Yanai, Y Zaizen, M Nishi, Y Inomata, K Kawakami, H Matsufuji, S Suenobu, N Handa, Kenichi Kohashi, Yoshinao Oda, Toshiro Hara, tomoaki taguchi, The prognostic significance of blastemal predominant histology in initially resected Wilms' tumors: A report from the Study Group for Pediatric Solid Tumors in the Kyushu Area, Japan.
, J Pediatr Surg. 2012 Dec;47(12):2205-9. , 2012.12.
562. Tatsuro Tajiri, O Kimura, S Fumino, T Furukawa, T Iehara, R Souzaki, YOSHIAKI KINOSHITA, Yuhki Koga, A Suminoe, Toshiro Hara, Kenichi Kohashi, Yoshinao Oda, T Hishiki, H Hosoi, E Hiyama, tomoaki taguchi, Surgical strategies for unresectable hepatoblastomas.
, J Pediatr Surg. 2012 Dec;47(12):2194-8. , 2012.12.
563. K Yokota, Akio Sakamoto, Yoshihiro Matsumoto, Shuichi Matsuda, Katsumi Harimaya, Yoshinao Oda, Yukihide Iwamoto, Clinical outcome for patients with dedifferentiated chondrosarcoma: a report of 9 cases at a single institute.
, J Orthop Surg Res. 2012 Dec 10;7(1):38. , 10, 7, 38, 2012.12.
564. M Takakura, Akira Yokomizo, Y Tanaka, M Kobayashi, G Jung, M Banno, T Sakuma, K Imada, Yoshinao Oda, M Kamita, K Honda, T Yamada, Seiji Naito, M Ono, Carbonic anhydrase I as a new plasma biomarker for prostate cancer.
, International Scholarly Research Network Oncology 2012 (2012) , 2012.12.
565. T Matsuura, Kenichi Kohashi, Y Yanagi, I Saeki, Makoto Hayashida, Shinichi Aishima, tomoaki taguchi, Yoshinao Oda, A morphological study of the removed livers from patients receiving living donor liver transplantation for adult biliary atresia.
, Pediatr Surg Int Dec;28(12):1171-1175, 2012, 2012.12.
566. Y Mori, Ohtsuka Takao, H Kono, T Aso, Y Nagayoshi, S Takahara, Masafumi Nakamura, K Ishigami, Shinichi Aishima, Yoshinao Oda, Masao Tanaka, Management strategy for multifocal branch duct intraductal papillary mucinous neoplasms of the pancreas.
, Pancreas Oct;41(7):1008-1012, 2012 (11th/ 12 authors), 2012.10.
567. Yoshihiro Ohishi, S Kurihara, Murasaki Aman, T Takeuchi, H Imamura, Tsunehisa Kaku, Hiroaki Kobayashi, Norio Wake, Yoshinao Oda, "Piling up" clear cells in müllerian-type mucinous and mixed cell-type borderline tumor do not represent concomitant clear cell neoplasms.
, Hum Pathol Oct;43(10):1618-1626, 2012 , 2012.10.
568. Kohei Nakata, Eishi Nagai, Y Miyasaka, K Ouchida, Ohtsuka Takao, Hiroki Toma, Minako Hirahashi, Shinichi Aishima, Yoshinao Oda, Masao Tanaka, The risk of lymph node metastasis in mucosal gastric carcinoma: especially for a mixture of differentiated and undifferentiated adenocarcinoma.
, Hepatogastroenterology. Sep;59(118):1855-8. 2012, 2012.09.
569. Yoshihiro Ohishi, Shuichi Kurihara, T Takeuchi, Murasaki Aman, Tsunehisa Kaku, Hiroaki Kobayashi, Norio Wake, Yoshinao Oda, E-cadherin nuclear staining is useful for the diagnosis of ovarian adult granulose cell tumor.
, Hum Pathol 43(6) June 808-817, 2012 , 2012.06.
570. Nokitaka Setsu, Kenichi Kohashi, Makoto Endo, Hidetaka Yamamoto, Yoshihiro Ohishi, K Sueyoshi, Yukihide Iwamoto, Masazumi Tsuneyoshi, T Motoi, A Kumagai, Yoshinao Oda, Inhibin alpha and synaptophysin immunoreactivity in synovial sarcoma with granular cell features.
, Hum Pathol 43(6) June 850-854, 2012 (Corresponding) , 2012.05.
571. Kenichi Kohashi, T Nakatsura, YOSHIAKI KINOSHITA, Hidetaka Yamamoto, Yuichi Yamada, Tatsuro Tajiri, Yukihide Iwamoto, tomoaki taguchi, Yoshinao Oda, Glypican 3 expression in tumors with loss of SMARCB1/INI1 protein expression., Hum Pathol 44(4): 526-533, 2013 (corresponding) , 2012.04.
572. Setsu N, Yamamoto H, Kohashi K, Endo M, Matsuda S, Yokoyama R, Nishiyama K, Iwamoto Y, Dobashi Y, Oda Y, The Akt/mammalian target of rapamycin pathway is activated and associated with adverse prognosis in soft tissue leiomyosarcomas.
, Cancer 118(6) Mar 15:1637-48, 2012 (corresponding), 2012.03.
573. Hashimoto K, Yamamaoto H, Shiratsuchi H, Nakashima T, Tamiya S, Nishiyama K, Higaki Y, Komune S, Tsuneyoshi T, Oda Y, HER2/neu gene amplification in ductal type of carcinoma ex pleomorphic adenoma in relation to the progression and prognosis: A chromogenic in situ hybridization (CISH) study.
, Histopathology. 2012 May;60(6B):E131-42. , 2012.03.
574. Morimatsu K, Aishima S, Kayashima T, Hayashi A, Nakata K, Oda Y, Taguchi T, Tsuneyoshi M, Tanaka M, Oda Y , Liver-Intestine cadherin expression is associated with intestinal differentiation and carcinogenesis in intraductal papillary-mucinous neoplasm.
, Pathobiology 79 (Feb): 107-114, 2012 (Corresponding) , 2012.02.
575. Fujita A, Yamamoto H, Imamura M, Nakamura N, Maehara Y, Tsuneyoshi M, Oda Y, Expression level of the mitotic checkpoint protein and G2-M cell cycle regulators and prognosis in gastrointestinal stromal tumors in the stomach.
, Virchows Arch Feb 460(2): 163-169, 2012 (corresponding) , 2012.02.
576. Shiota M, Song Y, Takeuchi A, Yokomizo A, Kashiwagi E, Kuroiwa K, Tatsugami K, Uchiumi T, Oda Y, Naito S, Antioxidant therapy alleviates oxidative stress by androgen deprivation and prevents conversion from androgen dependent to castration resistant prostate cancer.
, J Urol. 2012 Feb;187(2):707-14. , 2012.02.
577. Tajiri T, Souzaki R, Kinoshita Y, Yosue R, Kohashi K, Oda Y, Taguchi T, Surgical intervention strategies for pediatric ovarian tumors: experience with 60 cases at one institution.
, Pediatr Surg Int. 2012 Jan;28(1):27-31. , 2012.01.
578. Alatas FS, Masumoto K, Matsuura T, Hayashida M, Saeki I, Kohashi K, Oda Y, Taguchi T, Synchronized expressions of hepatic stellate cells and their transactivation and liver regeneration during liver injury in an animal model of cholestasis.
, J Pediatr Surg Dec;46(12):2284-2290, 2011 , 2011.12.
579. Souzaki R, Tajiri T, Teshiba R, Kinoshita Y, Yosue R, Kohashi K, Oda Y, Taguchi T , Correlation between the number of segmental chromosome aberrations and the age at diagnosis of diploid neuroblastomas without MYCN amplification.
, J Pediatr Surg Dec;46(12):2228-2232, 2011, 2011.12.
580. Nakata K, Ohuchida K, Mizumoto K, Kayashima T, Ikenaga N, Sakai H, Lin C, Fujita H, Otsuka T, Aishima S, Nagai E, Oda Y, Tanaka M, MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis.
, Surgery Nov;150(5): 916-922, 2011 , 2011.11.
581. Aishima S, Iguchi T, Fujita N, Taketomi A, Maehara Y, Masazumi Tsuneyoshi M, Oda Y, Histological and immunohistological findings in biliary intraepithelial neoplasia arising in a background of chronic biliary disease compared with liver cirrhosis of non-biliary aetiology.
, Histopathology 59(5) Nov; 867-875, 2011, 2011.11.
582. Fujita N, Aishima S, Iguchi T, Mano Y, Taketomi A, Shirabe K, Honda H, Tsuneyoshi M, Oda Y, Histological classification of microscopic portal venous invasion to predict prognosis in hepatocellular carcinoma.
, Hum Pathol 42(10): 1531-1538, 2011, 2011.10.
583. Song YH, Shiota M, Kuroiwa K, Naito S, Oda Y, The important role of glycine N-methyltransferase (GNMT) in the carcinogenesis and progression of prostate cancer.
, Mod Pathol 24(9) Sep: 1272-1280, 2011 (Corresponding), 2011.09.
584. Gushima M, Hirahashi M, Matsumoto T, Fujita K, Ohuchida K, Oda Y, Yao T, Iida M, Tsuneyoshi M, Possible role of activation-induced cytidine deaminase in ulcerative colitis-associated carcinogenesis.
, Histopathology 59(3) Sep; 460-469, 2011, 2011.09.
585. Fujiwara T, Fukushi J, Yamamoto S, Matsumoto Y, Setsu N, Oda Y, Yamada H, Okada S, Watari K, Ono M, Kuwano M, Kamura S, Iida K, Okada Y, Koga M, Iwamoto Y, Macrophage infiltration predicts poor prognosis for the human Ewing’s sarcoma family of tumors.
, Am J Pathol Sep; 179(3): 1157-1170, 2011, 2011.09.
586. Yamamoto H, Kojima A, Nagata S, Tomita Y, Takahashi S, Oda Y, KIT-negative gastrointestinal stromal tumor of the abdominal soft tissue: A clinicopathological and genetic study of 10 cases.
, Am J Surg Pathol 35(9): 1287-1295, 2011, 2011.09.
587. Matono H, Tamiya S, Yokoyama R, Saito T, Iwamoto Y, Tsuneyoshi M, Oda Y, Abnormalities of Wnt/beta-catenin signaling pathway induce tumor progression in sporadic desmoid tumoes: correlation between beta-catenin widespread expression and VEGF overexpression.
, Histopathology 59(3) Sep; 368-375, 2011 (Corresponding), 2011.09.
588. Tada Y, Yokomizo A, Shiota M, Song YH, Kashiwagi E, Kuroiwa K, Oda Y, Naito S , Ectonucleoside triphosphate diphosphohydrolase 6 expression in testis and testicular cancer and its implication in cisplatin resistance.
, Oncol Rep 26: 161-167, 2011 , 2011.07.
589. Shiota M, Takeuchi A, Song Y, Yokomizo A, Kashiwagi E, Uchiumi T, Kuroiwa K, Tatsugami K, Fujimoto N, Oda Y, Naito S, Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression.
, Endocr Relat Cancer. 2011 Jul 11;18(4):505-17. , 2011.06.
590. Endo M, Kobayashi C, Setsu N, Kohashi K, Yamamoto H, Tamiya S, Matsuda S, Iwamoto Y, Tsuneyoshi M, Oda Y, Prognostic significance of p14ARF, p15INK4b, and p16INK4a inactivation in malignant peripheral nerve sheath tumors: a comprehensive assessment of gene alteration, mRNA level and protein expression.
, Clin Cancer Res 17(11) Jun: 3771-3782, 2011 (corresponding), 2011.06, 軟部肉腫の中で比較的頻度の高い悪性末梢神経鞘腫瘍におけるp14,p15, p16遺伝子異常を解析したところ、これらの遺伝子異常が単発に起こる例に比較して、複数の異常を有する症例が有意に予後不良であることを明らかにした。.
591. Goto A, Hirahashi M, Osada M, Nakamura K, Yao T, Takayanagi R, Oda Y, Aberrant expression of activation-induced cytidine deaminase may associate with intestinal metaplasia and intestinalization of gastric cancer.
, Virchows Archiv 458 Jun: 717-724, 2011 , 2011.06.
592. Yamamoto H, Kohashi K, Imamura M, Kojima A, Oda Y, Yao T, Tsuneyoshi M, Heterozygosity loss at 22q and INI1 gene alteration in gastrointestinal stromal tumor.
, Pathobiology 78: 132-139, 2011 , 2011.05.
593. Maehata Y, Hirahashi M, Aishima S, Kishimoto J, Hirohashi S, Yao T, Takeshima H, Tsuneyoshi M, Oda Y, Significance of dysadherin and E-cadherin expression in differentiated-type gastric carcinoma with submucosal invasion.
, Hum Pathol 42(4): 558-562, 2011 (Corresponding) , 2011.04.
594. Nakata K, Ouchida K, Aishima S, Sadakari Y, Kayashima T, Miyasaka Y, Nagai E, Mizumoto K, Tanaka M, Tsuneyoshi M, Oda Y, Invasive carcinoma derived from intestinal-type intraductal papillary mucinous neoplasm is associated with minimal invasion, colloid carcinoma, and less invasive behavior, leading to a better prognosis.
, Pancreas 40(4): 581-587, 2011 , 2011.04.
595. Shiota M, Tsunoda T, Song Y-H, Yokomizo A, Tada Y, Oda Y, Naito S , Enhanced S100P expression sensitizes human bladder cancer cells to cisplatin.
, Br J Urol Int 107(7): 1148-1153, 2011 , 2011.04.
596. Aishima S, Fujita N, Mano Y, Kubo Y, Tanaka Y, Taketomi A, Shirabe K, Maehara Y, Oda Y, Different roles of S100P overexpression in intrahepatic cholangiocarcinoma: Carcinogenesis of perihilar type and aggressive behavior of peripheral type
, Am J Surg Pathol 35(4): 590-598, 2011, 2011.04.
597. Yan X, Takahara M, Xie L, Gondo C, Oda Y, Nakahara T, Uchi H, Takeuchi S, Tu Y, Moroi Y, Furue M, Stromal expression of cathepsin K in squamous cell carcinoma
, J Eur Acad Dermatol and Venereology 25(3): 362-365, 2011, 2011.03.
598. Hashimoto K, Yamamaoto H, Shiratsuchi H, Nakashima T, Tamiya S, Higaki Y, Tsuneyoshi M, Komune S, Oda Y, S100P expression is associated with the early steps in the malignant transformation of pleomorphic adenoma.
, Am J Surg Pathol 35(3): 346-355, 2011 , 2011.03.
599. Amamoto R, Uchiumi T, Song YH, Yagi M, Oda Y, Tsuneyoshi T, Naitoh S, Yokomizo A, Tokunaga S, Kang D, Mitochondrial p32/C1QBP is highly expressed in prostate cancer and is associated with shorter PSA relapse time after radical prostatectomy.
, Cancer Sci 102(3): 639-647, 2011 , 2011.03.
600. Yan X, Takahara M, Xie L, Gondo C, Oda Y, Setsu N, Takeuchi S, Tu Y, Moroi Y, Furue M, Arginine metabolism in soft tissue sarcoma
, J Dermatol Sci 61(3): 211-215, 2011 , 2011.03.
601. Fujita K, Yamamoto H, Matsumoto T, Hirahashi M, Gushima M, Kishimoto J, Nishiyama K, Taguchi T, Yao T, Oda Y, Sessile serrated adenoma with early neoplastic progression: A clinicopathological and molecular study.
, Am J Surg Pathol 35(2): 295-304, 2011 , 2011.02.
602. Nishimura I, Ohishi Y, Oda Y, Kishimoto J, Yasunaga M, Ohkuma E, Kobayashi H, Wake N, Tsuneyoshi M, Expression and localization of E-cadherin and beta-catenin in uterine carcinosarcoma.
, Virchow Archiv 458(1): Jan 85-94, 2011 , 2011.01.
603. Fujita K, Hirahashi M, Matsumoto T, Gushima M, Oda Y, Kishimoto J, Yao T, Iida M, Tsuneyoshi M, Mucin core protein expression in serrated polyps of the large intestine.
, Virchow Arch 457: 443-449, 2010 , 2010.12.
604. Souzaki R, Tajiri T, Souzaki M, Kinoshita Y, Tanaka S, Kohashi K, Oda Y, Katano M, Taguchi T, Hedgehog signaling pathway in neuroblastoma differentiation
, J Pediat Surg 45(12):2299-304, 2010 , 2010.12.
605. Shiota M, Song Y, Yokomizo A, Kiyoshima K, Tada Y, Uchino H, Uchiumi T, Inokuchi J, Oda Y, Kuroiwa K, Tatsugami K, Naito S, Foxo3a suppression of urothelial cancer invasiveness through Twist1, Y-boxbinding protein 1 and E-cadherin regulation
, Clin Cancer Res Dec 1, 16(23): 5654-63, 2010 , 2010.12.
606. Hayashi A, Aishima S, Miyasaka Y, Nakata K, Morimatsu K, Oda Y, Nagai E, Oda Y, Tanaka M, Tsuneyoshi M, Pdcd4 expression in intraductal papillary mucinous neoplasm of the pancreas: its association with tumor progression and proliferation.
, Hum Pathol 41(11): 1507-1515, 2010, 2010.11.
607. Yamamoto H, Kojima A, Miyasaka Y, Imamura M, Nakamura N, Yao T, Tsuneyoshi M, Oda Y, Prognostic impact of blood vessel invasion in gastrointestinal tumor of the stomach.
, Hum Pathol 41(10): 1422-1430, 2010, 2010.10.
608. Ohishi Y, Oda Y, Kurihara S, Kaku T, Yasunaga M, Kobayashi H, Wake N, Tsuneyoshi M, Nuclear localization of E-cadherin but not beta-catenin in human ovarian granulosa cell tumours and normal ovarian follicles and ovarian stroma.
, Histopathology 58(3): 423-432, 2011 , 2010.09.
609. Kohashi K, Oda Y, Yamamoto H, Tamiya S, Matono H, Iwamoto Y, Taguchi T, Tsuneyoshi M, Reduced expression of SMARCB1/INI1 protein in synovial sarcoma.
, Mod Pathol 23(7): 981-990, 2010 (Corresponding), 2010.07.
610. Nakata K, Nagai E, Ohuchida K, Hayashi A, Miyasaka Y, Aishima S, Oda Y, Mizumoto K, Tanaka M, Tsuneyoshi M, S100P is a novel marker to identify intraductal papillary mucinous neoplasms.
, Hum Pathol 41(6): 824-831, 2010, 2010.06.
611. Yan X, Takahara M, Dogu L, Xie L, Gondo C, Endo M, Oda Y, Nakahara T, Uchi H, Takeuchi S, Tu Y, Moroi Y, Furue M , Expression of catepsin K in neurofibromatosis 1-associated cutaneous malignant peripheral nerve sheath tumors and neurofibromas.
, J Dermatol Sci 58(3): 227-229, 2010., 2010.06.
612. Fujita N, Aishima S, Iguchi T, Nishihara Y, Yamamoto H, Taketomi A, Oda Y, Honda H, Tsuneyoshi M, Down-regulation of artery in moderately differentiated hepatocellular carcinoma related to tumor development.
, Hum Pathol 41(6): 838-847, 2010, 2010.06.
613. Hayashi A, Aishima S, Inoue T, Nakata K, Morimatsu K, Oda Y, Tanaka M, Tsuneyoshi M, Decreased expression of focal adhesion kinase is associated with a poor prognosis in extrahepatic bile duct carcinoma.
, Hum Pathol 41(6): 859-866, 2010, 2010.06.
614. Okuma E, Ohishi Y, Oda Y, Aishima S, Kobayashi H, Wake N, Tsuneyoshi M, Cytoplasmic and stromal localization of laminin gamma 2 chain promotes destructive and infiltrative invasion in ovarian mucinous neoplasms of gastro-intestinal type.
, Oncol Rep 24(6): 1569-1576, 2010 , 2010.06.
615. Tashiro A; Takeuchi S; Nakahara T, Oba J; Tsujita J; Fukushi J; Kiryu H; Oda Y; Xie L; Yan X; Takahara M; Moroi Y; Furue M, Aberrant expression of CD10 in ground-glass-like multinucleated giant cells of multicentric reticulohistiocytosis.
, J Dermatol 24(6): 995-997, 2010 , 2010.06.
616. Shiota M, Song Y, Yokomizo A, Tada Y, Kuroiwa K, Inokuchi J, EtoM, Oda Y, Uchiumi T, Fujimoto N, Seki N, Naito S, Human heterochromatin protein 1 isoform HP1β promotes prostate cancer growth through androgen receptor activation.
, Endocr Relat Cancer 17(2): 455-467, 2010, 2010.05.
617. Dugu L, Hayashida S, Nakahara T, Xie L, Iwashita Y, Liu X, Uchi H, Tateuchi S, Takahara M, Oda Y, Moroi Y, Furue M, Aberrant expression of tenascin-c and neuronatin in malignant peripheral nerve sheath tumors.
, Eur J Dermatol. 20(5): 1-5, 2010 , 2010.05.
618. Matsuura S, Oda Y, Matono H, Izumi T, Yamamoto H, Tamiya S, Iwamoto Y, Tsuneyoshi M:, Overexpression of ADAM28 is correlated with high histological grade in conventional chondrosarcoma: a helpful tool for evaluation of cartilaginous bone tumors with a spectrum between low-grade chondrosarcoma and enchondroma.
, Hum Pathol 41(3): 343-351, 2010 (Corresponding) , 2010.03.
619. Song YH, Oda Y, Hori M, Kuroiwa K, Ono M, Hosoi F, Basaki Y, Kuwano M, Naito S, Tsuneyoshi M:, N-myc downstream regulated gene 1 (NDRG1)/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin.
, Hum Pathol 41(2): 214-222, 2010 (Corresponding), 2010.02.
620. Kurihara S, Oda Y, Ohishi Y, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M, Coincident expression of β-catenin and cyclin D1 as a contrasting feature of the traditional category "high-grade endometrial stromal sarcoma: analysis of the Wnt signalling pathway in 37 cases of endometrial stromal and related tumors.
, Mod Pathol 23(2): 225-234, 2010 (Corresponding) , 2010.02.
621. Yamamoto H, Yamaguchi H, Aishima S, Oda Y, Kohashi K, Oshiro Y, Tsuneyoshi M , Inflammatory myofibroblastic tumor versus IgG4-related sclerosing disease and
inflammatory pseudotumor: A comparative clinicopathological study.

, Am J Surg Pathol 33(9): 1330-1340, 2009, 2009.09.
622. Zhao Y, Zhang CL, Zeng BF, Wu XS, Gao TT, Oda Y, Enhanced chemosensitivity of drug-resistant osteosarcoma cells by lentivirus-mediated Bcl-2 silencing.

, Biochem Biophys Res Commun 390(3): 642-647, 2009, 2009.09.
623. Ohishi Y, Oda Y, Kurihara S, Kaku T, Yasunaga M, Nishimura I, Okuma E, Kobayashi H, Wake N, Tsuneyoshi M , Hobnail-like cells in serous borderline tumor do not represent concomitant incipient clear cell neoplasms.
, Hum Pathol 40(8): 1168-1175, 2009, 2009.08.
624. Nakata K, Ohuchida K, Nagai E, Hayashi A, Miyasaka Y, Kayashima T, Yu J, Aishima S, Oda Y, Mizumoto K, Tanaka M, Tsuneyoshi M , LMO2 is a novel predictive marker for a better prognosis in pancreatic cancer.

, Neoplasia 11(7): 712-719, 2009 , 2009.07.
625. Yasunaga M, Ohishi Y, Oda Y, Misumi M, Kobayashi H, Wake N, Tsuneyoshi M , Immunohistochemical characterization of mullelian mucinous borderline tumor (MMBT): A possible link between MMBT and serous borderline tumor (SBT) and low-grade endometrioid adenocarcinoma (LG-EC) in immunophenotype.
, Hum Pathol 40(7): 965-974, 2009, 2009.07.
626. Yamamoto H, Tobo T, Nakamori M, Imamura M, Kojima A, Oda Y, Nakamura N, Takahira T, Yao T, Tsuneyoshi M , Neurofibromatosis type 1-related gastrointestinal stromal tumors: A special reference to loss of heterozygosity at 14q and 22q.
, J Cancer Res Clin Oncol 135(6): 791-798, 2009. , 2009.06.
627. Naka T, Boltze C, Samii A, Samii M, Herold C, Ostertag H, Iwamoto Y, Oda Y, Tsuneyoshi M, Kuester D, Roessner A , Expression of c-MET, low-molecular-weight cytokeratin, matrix metalloproteinases-1 and -2 in spinal chordoma.
, Histopathology 54(5): 607-613, 2009. , 2009.05.
628. Segawa Y, Oda Y, Yamamoto H, Shiratsuchi H, Hirakawa N, Komune S, Tsuneyoshi M , Close correlation between CXCR4 and VEGF expression and their prognostic implications in nasopharyngeal carcinoma.
, Oncol Rep 21(5): 1197-1202, 2009. (Corresponding) , 2009.05.
629. Aoki D, Oda Y, Hattori S, Taguchi K, Ohishi Y, Basaki Y, Oie S, Suzuki N, Kono S, Tsuneyoshi M, Ono M, Yanagawa T, Kuwano M , Overexpression of class III beta-tubulin predicts good response for taxan-based chemotherapy in ovarian clear cell adenocarcinoma.
, Clin Cancer Res 15 (4): 1473-1480, 2009. , 2009.04.
630. Oda Y, Tateishi N, Matono H, Matsuura S, Yamamaoto H, Tamiya S, Yokoyama R, Matsuda S, Iwamoto Y, Tsuneyoshi M , Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft-tissue sarcoma.
, Int J Cancer 124: 1852-1859, 2009. (Corresponding) , 2009.04.
631. Itakura E, Yamamoto H, Oda Y, Furue M, Tsuneyoshi M , VEGF-C and VEGFR-3 in a series of lymphangiomas: Is superficial lymphangioma a true lymphangioma?
, Virchow Arch 454(3): 317-325, 2009. (Corresponding) , 2009.03.
632. Kohashi K, Oda Y, Izumi T, Yamamoto H, Tamiya S, Tsuneyoshi M , Infrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: A useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor.
, Hum Pathol 40 (3): 349-355, 2009. (Corresponding) , 2009.03.
633. Maruta S, Takiguchi S, Ueyama M, Kataoka Y, Oda Y, Tsuneyoshi M, Iguchi H , A role of leukemia inhibitory factor in melanoma-induced bone metastasis.
, Clin Exp Metastasis 26 (2): 133-141, 2009. , 2009.02.
634. Fujii K, Miyashita K, Yamada Y, Eguchi T, Taguchi K, Oda Y, Oda S, Yoshida MA, Tanaka M , Tsuneyoshi M: , Simulation-based analyses reveal stable microsatellite sequences in human pancreatic cancer.
, Cancer Genet Cytogen 189(1): 5-14, 2009. , 2009.01.
635. Sakamoto A, Akieda S, Oda Y, Iwamoto Y, Tsuneyoshi M: , Mutation analysis of the Gadd45 gene at exon 4 in atypical fibroxanthoma.
, BMC Dermatology 9 (1): 1, 2009. (online journal) , 2009.01.
636. Iwasa A, Oda Y, Kurihara S, Ohishi Y, Yasunaga M, Nishimura I, Takagi E, Kobayashi H, Wake N, Tsuneyoshi M , Malignant transformation of mature cystic teratoma to squamous cell carcinoma involves altered expression of p53- and p16/Rb-dependent cell-cycle-regulator proteins
, Pathol Int 56 (12): 757-764, 2008. (Corresponding) , 2008.12.
637. Matono H, Oda Y, Nakamori M, Tamiya S, Yamamoto H, Izumi T, Matsuura S, Yokoyama R, Saito T, Tanaka K, Iwamoto Y, Tsuneyoshi M: , Correlation between beta-catenin widespread nuclear expression and matrix
metalloprotease-7 overexpression in sporadic desmoid tumors.
, Hum Pathol 39(12): 1802-1808, 2008. (Corresponding) , 2008.12.
638. Nakamori M, Oda Y, Kurihara S, Tsuneyoshi M: , Clinicopathological and immunohistochemical study of extrapleural and pleural solitary
fibrous tumors: A special emphasis on comparison between ordinary tumor and malignant variant.
, Molecular Medicine Reports 1: 797-803, 2008. (Corresponding) , 2008.12.
639. Yabuuchi H, Matsuo Y, Kamitani T, Setoguchi T, Okafuji T, Soeda H, Sakai S, Hatakenaka M, Nakashima T, Oda Y, MD, Honda H , Parotid gland tumors: Can addition of diffusion-weighted MR imaging to dynamic contrast-enhanced MR imaging improve diagnostic accuracy in characterization?
, Radiology 249 (3): 909-916, 2008. , 2008.11.
640. Kohashi K, Oda Y, Yamamoto H, Tamiya S, Takahira T, Kobayashi C, Takahashi Y, Taguchi T, Suita S, Tsuneyoshi M, Alterations of RB1 gene in embryonal and alveolar rhabdomyosarcoma: Special
reference to utility of pRB immunoreactivity in differential diagnosis of
rhabdomyosarcoma subtype. Alterations of RB1 gene in each subtype of
rhabdomyosarcoma.
, J Cancer Res Clin Oncol 134(10): 1097-1103, 2008 (Corresponding), 2008.10.
641. Kohashi K, Oda Y, Yamamoto H, Tamiya S, Oshiro Y, Izumi T, Taguchi T, Tsuneyoshi M, SMARCB1/INI1 protein expression in round cell sarcomas associated with chromosomal translocations involving EWS: A special reference of SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma.
, Am J Surg Pathol 32(8):1228-38, 2008 (Corresponding), 2008.08.
642. Kurihara S, Oda Y, Ohishi Y, Iwasa A, Takahira T, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M, Endometrial stromal sarcomas and related high-grade sarcomas:
Immunohistochemical and molecular genetic study of 31 cases.
, Am J Surg Pathol 32(8):1228-38, 2008 (Corresponding), 2008.08.
643. Migita T, Oda Y, Masuda K, Hirata A, Kuwano M, Naito S, Tsuneyoshi M, Inverse relationship between E-cadherin and p27kip1 expression in renal cell carcinoma.
, Int J Oncol 33(1): 41-47, 2008. (Corresponding) , 2008.07.
644. Oda Y, Kohashi K, Yamamoto H, Tamiya S, Kohno K, Kuwano M, Iwamoto Y, Tajiri T, Taguchi T, Tsuneyoshi M: , Different expression profiles of Y-box-binding protein-1 and multidrug
resistance-associated proteins between alveolar and embryonal rhabdomyosarcoma.
, Cancer Sci 99(4): 726-732, 2008 (Corresponding) , 2008.04.
645. Segawa Y, Oda Y, Yamamoto H, Tomita K, Yamada T, Komune S, Tsuneyoshi M, Overexpression of inducible nitric oxide synthase in nasopharyngeal carcinoma: its
special reference to p53 gene alterations and oxidative stress analyzed by
immunohistochemical and molecular methods.
, Histopathology 52(2): 213-223, 2008 (Corresponding) , 2008.01.
646. Itakura E, Yamamoto H, Oda Y, Tsuneyoshi M, Detection and characterization of vascular endothelial growth factors and their receptors in a series of angiosarcomas., J Surg Oncol 97(1): 74-81, 2008 , 2008.01.
647. Hatakenaka M, Soeda H, Yabuuchi H, Matsuo Y, Kamitani T, Oda Y, Tsuneyoshi M, Honda H , Apparent diffusion coefficients of breast tumors: Clinical application
, Magn Reson Med Sci 7 (1): 23-29, 2008. , 2008.01.
648. Nakagawa M, Oda Y, Eguchi T, Aishima S, Yao T, Hosoi F, Oie S, Ono M, Kuwano M, Tanaka M, Tsuneyoshi M, Expression profile of class I histone deacetylases in human cancer tissues.
, Oncol Rep 18(4), Oct: 769-774, 2007 (Corresponding), 2007.10.
649. Iwasa A, Oda Y, Ohishi Y, Kaneki E, Kurihara S, Yamada T, Hirakawa T, Wake N, Tsuneyoshi M, Squamous cell carcinoma arising in mature cystic teratoma of the ovary; An
immunohistochemical and molecular analysis for its tumorigenesis., Histopathology 51(1): 98-104, 2007 (Corresponding) , 2007.07.
650. Oda Y, Ohishi Y, Basaki Y, Kobayashi H, Hirakawa T , Wake N, Ono M, Nishio K, Kuwano M, Tsuneyoshi M, Prognostic implication of the nuclear localization of the Y-box-binding protein-1 and CXCR4 expression in ovarian cancer: Their correlation with activated Akt, LRP/MVP and P-glycoprotein expression, Cancer Sci 98(7): 1020-1026, 2007 (Corresponding), 2007.07.
651. Kohashi K, Oda Y, Yamamto H, Tamiya S, Izumi T, Ohta S, Taguchi T, Suita S, Tsuneyoshi M, Highly aggressive behavior in malignant rhabdoid tumor: A special reference to
SMARCB1/INI1 gene alterations using molecular genetic analysis including
quantatative real-time PCR., J Cancer Res Clin Oncol 133(1) : 817-824, 2007 (Corresponding), 2007.07.
652. Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M, Frequent immunoexpression of TGF-beta1, FGF-2 and BMP-2 in fibroblast-like cells in osteofibrous dysplasia., Oncol Rep 17; 531-535, 2007., 2007.07.
653. Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M, Expression of UV-induced molecule of Gadd45 in atypical fibroxanthoma., Histopathology 50(7): 939-941, 2007, 2007.07.
654. Li Y, Tanaka K, Li X, Okada T, Nakamura T, Takasaki M, Yamamoto S, Oda Y, Tsuneyoshi M, Iwamoto Y , Cyclin-dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits tumor growth in drug-resistant osteosarcoma and Ewing’s family tumor cells.
, Int J Cancer 121(6): 1212-1218, 2007, Int J Cancer 121(6): 1212-1218, 2007, 2007.07.
655. Takahira T, Oda Y, Higaki K, Tamiya S, Yamamoto H, Kobayashi C, Izumi T, Iwamoto Y, Tsuneyoshi M, Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB expresssion in dermatofibrosarcoma protuberans., Mod Pathol 20(6): 668-675, 2007 (Corresponding), 2007.06.
656. Oda Y, Izumi T, Harimaya K, Segawa Y, Ishihara S, Komune S, Iwamoto Y, Tsuneyoshi M, Pigmented villonodular synovitis with chondroid metaplasia, resembling
chondroblastoma of the bone. A report of three cases., Mod Pathol 20; 545-551, 2007 (Corresponding), 2007.05.
657. Hori H, Oda Y, Kiyoshima K, Yamada Y, Nakashima Y, Naito S, Tsuneyoshi M, Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in the patients on dialysis., J Pathol 212: 218-226, 2007 (Corresponding), 2007.05.
658. Imamura M, Yamamoto H, Nakamura N, Oda Y, Yao T, Kakeji Y, Baba H, Maehara Y, Tsuneyoshi M, Expression of VEGF is associated with tumor progression and KIT genotype in
gastrointestinal stromal tumor., Mod Pathol, Mod Pathol 20; 529-592, 2007., 2007.05.
659. Ohishi Y, Oda Y, Basaki Y, Kobayashi H, Wake N, Kuwano M, Tsuneyoshi M, Expression of beta-tubulin isotypes in human primary ovarian carcinomas.
, Gynecol Oncol 105; 586-592, 2007 (Corresponding), 105; 586-592, 2007. , 2007.04.
660. Basaki Y, Hosoi F, Oda Y, Fotovati A, Ono M, Izumi H, Kohno K, Sakai K, Shimoyama T, Nishio K, Kuwano M, Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells, Oncogene 26; 2736-2746, 2007 , Oncogene 26; 2736-2746, 2007, 2007.04.
661. Inoue T, Eguchi T, Oda Y, Nishiyama K, Fujii K, Izumi H, Kohno K, Yamaguchi K, Tanaka M, Tsuneyoshi M, Expression of GalNAc-T3 and its relationships with clinicopathological factors in 61extrahepatic bile duct carcinomas analyzed using stepwise sections: Special reference to its association with lymph node metastases., Mod Pathol 20; 267-276, 2007., 2007.01.
662. Izumi T, Oda Y, Hasegawa T, Kawai A, Sonobe H, Nakanishi Y, Takahira T, Kobayashi C, Yamamoto H, Tamiya S, Yokoyama R, Hirohashi S, Iwamoto Y, Tsuneyoshi M, Dysadherin expression as a significant prognostic factor and as a determinant of histological features in synovial sarcoma: special reference to its inverse relationship with E-cadherin expression., Am J Surg Pathol 31; 85-94, 2007. (Corresponding), 2007.01.
663. Saito T, Oda Y, Yamamoto H, Kawaguchi K, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M, Nuclear beta-catenin correlates with cyclin D1 expression in spindle and
pleomorphic sarcomas but not in synovial sarcoma., Hum Pathol 37; 689-697, 2006. (Corresponding), 2006.10.
664. Aishima S, Basaki Y, Oda Y, Kuroda Y, Nishihara Y, Taguchi K, Taketomi A, Maehara Y, Hosoi F, Maruyama Y, Fotovati A, Oie S, Ono M, Ueno T, Sata M, Yano H, Kojiro M, Kuwano M, Tsuneyoshi M, High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma., Cancer Sci 97; 1182-1190, 2006., 2006.10.
665. Kusumoto H, Haraguchi M, Nozuka Y, Oda Y, Tsuneyoshi M, Iguchi H, Characteristic features of disseminated carcinomatosis of the bone marrow due to
gastric cancer: The pathogenesis of bone destruction.
, Oncol Rep 16; 735-40, 2006, 2006.10.
666. Yamamoto H, Oda Y, Tamiya S, Takahashi Y, Kinoshita Y, Ishizawa S, Kubota M, Tsuneyoshi M, Are human herpesvirus-8 and Epstein-Barr virus present in inflammatory
myofibroblastic tumor with the ALK fusion gene?, Pathol Int 56; 584-590, 2006., 2006.10.
667. Oda Y, Yamamoto H, Tamiya S, Matsuda S, Tanaka K, Yokoyama R, Iwamoto Y, Tsuneyoshi M:, CXCR4 and VEGF expression in the primary site and the metastatic site of human
osteosarcoma: Analysis within a group of patients, all of whom developed lung
metastasis., Mod Pathol 19: 738-45, 2006. (corresponding), 2006.08.
668. Kiyoshima K, Oda Y, Tamiya S, Hori Y, Yamada T, Naito S, Tsuneyoshi M:, What factors impact on prostatic contour alterations? Histological analysis of altered prostatic contours; especially an association with prostate adenocarcinoma., Pathol Int 56; 390-396, 2006. (Corresponding), 2006.06.
669. Oda Y, Tsuneyoshi M, Extrarenal rhabdoid tumors of soft parts: Clinicopathologic and molecular genetic review and distinction from other soft tissue sarcomas with rhabdoid feature., Pathol Int 56: 287-295, 2006. (Corresponding), 2006.06.
670. Matsunobu T, Tanaka K, Nakamura T, Nakatani F, Sakimura R, Hanada M, Li X, Okada T, Oda Y, Tsuneyoshi M, Iwamoto Y, The possible role of EWS-Fli1 in evasion of sequence in Ewing family tumors.
Cancer Res 66; 803-11, 2006., Cancer Res 66; 803-11, 2006., 2006.01.
671. Okada T, Tanaka K, Nakatani F, Sakimura R, Matsunobu T, Li X, Hanada M, Nakamura T, Oda Y, Tsuneyoshi M, Iwamoto Y, Involvement of P-glycoprotein and MRP1 in resistance to cyclic tetrapeptide
subfamily of histone deacetylase inhibitors in the drug-resistant osteosarcoma and Ewing's sarcoma cells., Int J Cancer 118; 90-97, 2006, 2006.01.
672. Kobayashi C, Oda Y, Takahira T, Izumi T, Kawaguchi K, Yamamoto H, Tamiya S, Oda S, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M:, Chromosomal and microsatellite instability of malignant peripheral nerve sheath
tumors: The study of 10 tumors from 9 patients., Cancer Genet Cytogen 165; 98-105, 2006 (Corresponding), 2006.01.
673. Kobayashi C, Oda Y, Takahira T, Izumi T, Kawaguchi K, Yamamoto H, Tamiya S, Yamada T, Iwamoto Y, Tsuneyoshi M, Aberrant expression of CHFR in malignant peripheral nerve sheath tumors., Mod Pathol 19: 524-532, 2006 (Corresponding), 2006.01.
674. Kusumoto H, Haraguchi M, Nozuka Y, Oda Y, Tsuneyoshi M, Iguchi H, Characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer: The pathogenesis of bone destruction., Oncol Rep 16; 735-40, 2006., 2006.01.
675. Kiyoshima K, Oda Y, Naito S, Tsuneyoshi, M:, Overexpression of laminin -5 gamma 2 chain and its prognostic significance in
urothelial carcinoma of urinary bladder: Association with expression of COX-2, EGFR,and HER2., Hum Pathol, 36; 522-530, 2005 (Corresponding), 10.1016/j.humpath.2005.02.013, 36, 5, 522-530, 2005.01.
676. Uryu H, Oda Y, Shiratsuchi H, Oda S, Yamamoto H, Komune S, Tsuneyoshi M:, Microsatellite instability, proliferating activity and cytokeratin profiles in sinonasal carcinoma: molecular genetic and immunohistochemical comparison with oral squamous cell carcinoma., Oncology Rep 14; 1133-1142, 2005. (Corresponding), 2005.01.
677. Kawaguchi K, Oda Y, Takahira T, Saito T, Yamamoto H, Kobayashi C, Tamiya S,Oda S, Iwamoto Y, Tsuneyoshi M:, Microsatellite instability and hMLH1 and hMSH2 expression analysis in soft tissue sarcomas., Oncology Rep 13: 241-246, 2005 (Corresponding), 13, 2, 241-246, 2005.01.
678. Naka T, Boltze C, Schulz T-O, Samii A, Herold C, Ostertag H, Iwamoto Y, Oda Y, Tsuneyoshi M, Roessner A:, Intralesional Fibrous Septum in Chordoma: A Clinicopathologic and
Immunohistochemical Study of 122 Lesions., Am J Clin Pathol 124; 288-294, 2005, 2005.01.
679. Naka T, Boltze C, Kuester D, Samii A, Herold C, Ostertag H, Iwamoto Y, Oda Y,, Histogenesis of intralesional fibrous septum in chordoma., Pathol Res Pract 201; 443-447, 2005., 10.1016/j.prp.2005.05.007, 201, 6, 443-447, 2005.01.
680. Kawaguchi K, Oda Y, Saito T, Takahira T, Yamamoto H, Tamiya S, Iwamoto Y, Tsuneyoshi M:, Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas., Hum Pathol 36; 357-363, 2005 (Corresponding), 10.1016/j.humpath.2005.01.017, 36, 4, 357-363, 2005.01.
681. Takahira T, Oda Y, Tamiya S, Yamamoto H, Kobayashi C, Izumi T, Ito K, Iwamoto Y, Tsuneyoshi M:, Alterations of the RB1 gene in dedifferentiated liposarcoma., Mod Pathol 18: 1461-1470, 2005 (corresponding)., 10.1038/modpathol.3800447, 18, 11, 1461-1470, 2005.01.
682. Nakamura N, Yamamoto H, Yao T, Oda Y, Nishiyama K, Imamura K, Yamada T, Nawata H, Tsuneyoshi M:, Prognostic significance of abnormalities of cell-cycle regulatory proteins in
gastrointestinal stromal tumor and relevance of the risk-grading system., Hum Pathol 36; 828-837, 2005, 2005.01.
683. Oda Y, Yamamoto H, Takahira T, Kobayashi C, Kawaguchi K, Tateishi N, Nozuka Y, Tamiya S, Tanaka K, Matsuda S, Yokoyama R, Iwamoto Y, Tsuneyoshi M:, Frequent alteration of p16INK4a/p14ARF and p53 pathways of round cell
appearance in myxoid/round cell liposarcoma: Altered p53 gene and reduced
p14ARF expression correlates with poor prognosis., J Pathol 207; 410-421, 2005. (Corresponding), 10.1002/path.1848, 207, 4, 410-421, 2005.01.
684. Oda Y, Saito T, Tateishi N, Ohishi Y, Tamiya S, Yamamoto H, Yokoyama R, Uchiumi T, Iwamoto Y, Kuwano M, Tsuneyoshi M, ATP-binding cassette superfamily transporter gene expression in human soft tissue sarcoma., Int J Cancer 114: 854-862, 2005 (Corresponding), 10.1002/ijc.20589, 114, 6, 854-862, 2005.01.
685. Kuwano M, Oda Y, Izumi H, Yang S-J, Uchiumi T, Iwamoto Y, Toi M, Fujii T,Yamana H, Kinoshita H, Kamura T, Tsuneyoshi M, Yasumoto K, Kohno K, The role of nuclear Y-box binding protein 1 as a global marker in drug resistance., Mol Cancer Ther 3; 1485-92, 2004, 3, 11, 1485-1492, 2004.01.
686. Matsunobu T, Tanaka K, Matsumoto Y, Nakatani F, Sakimura R, Hanada M, Li X, Oda Y, Naruse I, Hoshino H, Tsuneyoshi M, Miura H, Iwamoto Y, The Prognostic and therapeutic relevance of p27kip1 in Ewing's family tumors., Clin Cancer Res 10; 1003-1012, 2004., 10.1158/1078-0432.CCR-0788-3, 10, 3, 1003-1012, 2004.01.
687. Kawaguchi K, Oda Y, Saito T, Yamamoto H, Tamiya S, Takahira T, Iwamoto Y, Tsuneyoshi M:, Promoter methylation or homozygous deletion associated with a loss of
death-associated protein kinase expression in leiomyosarcoma of soft tissue., Hum Pathol 35: 1266-1271, 2004 (Corresponding), 2004.01.
688. Saito T, Oda Y, Kawaguchi K, Takahira T, Yamamoto H, Tanaka K, Matsuda S, Sakamaoto A, Iwamoto Y, Tsuneyoshi M:, PTEN and other tumor supressor gene mutations as secondary genetic
alterations in synovial sarcoma., Oncol Reports 11; 1011-1015, 2004., 11, 5, 1011-1015, 2004.01.
689. Kaneki E, Oda Y, Ohishi Y, Tamiya S, Oda S, Hirakawa T, Nakano H, Tsuneyoshi M:, Frequent microsatellite instability in synchronous ovarian and endometrial
adenocarcinoma and usefullness for differential diagnosis., Hum Pathol 35: 1484-1493, 2004 (Corresponding), 10.1016/j.humpath.2004.08.011, 35, 12, 1484-1493, 2004.01.
690. Kawaguchi K, Oda Y, Saito T, Tamiya S, Yamamoto H, Matsuda S, Tanaka K, Iwamoto Y, Tsuneyoshi M, Decreased expression of TGF-b II receptor associates with that of p27/kip1 in
giant cell tumor of bone: A possible link between TGF-b and cell cycle-related
protein., Hum Pathol, 10.1016/S0046-8177(03)00470-2, 35, 1, 61-68, 35; 61-68, 2004, 2004.01.
691. Kiyoshima K, Yokomizo A, Yoshida T, Tomita K, Naito S, Nakamura M, Yonemasu H, Oda Y, Hasegawa Y, Anatomical features of periprostatic tissue and its surroundings: A histological analysis of 79 radical retropubic prostatectomy specimens., Jpn J Clin Oncol 34; 463-468, 2004, 10.1093/jjcolhyh078, 34, 8, 463-468, 2004.01.
692. Takahira T, Oda Y, Tamiya S, Yamamoto H, Kawaguchi K, Kobayashi C, Iwamoto Y, Tsuneyoshi M:, Alterations of the p16INK4a/ p14ARF pathway in clear cell sarcoma., Cancer Science 95; 651-655, 2004 (Corresponding), 10.1111/j.1349-7006.2004.tb03324.x, 95, 8, 651-655, 2004.01.
693. Takahashi Y, Oda Y, Kawaguchi K, Tamiya S, Yamamoto H, Suita S, Tsuneyoshi M:, Alteratered expression and molecular abnormalities of cell-cycle reguratory
proteins in rhabdomyosarcoma., Mod Pathol 17; 660-669, 2004 (Corresponding), 2004.01.
694. Yamamoto H, Oda Y, Kawaguchi K, Nakamura N, Oshiro Y, Tsuneyoshi M, c-kit mutation in extragastrointestinal stromal tumor (gastrointestinal stromal
tumor of the soft part)., Am J Surg Pathol 28; 479-488, 2004, 10.1097/00000478-200404000-00007, 28, 4, 479-488, 2004.01.
695. Takahira T, Oda Y, Tamiya S, Yamamoto H, Kawaguchi K, Oda S, Iwamoto Y, Tsuneyoshi M, Microsatellite instability and p53 mutation associate with tumor progression in
dermatofibrosarcoma protuberans., Hum Pathol 35; 240-245, 2004, 10.1016/j.humpath.2003.09.016, 35, 2, 240-245, 2004.01.
696. Oda Y, Takahira T, Kawaguchi K, Yamamoto H, Tamiya S, Matsuda S, Tanaka K,wamoto Y, Tsuneyoshi M:, Low-grade fibromyxoid sarcoma versus low-grade myxofibrosarcoma in the
extremities and trunk. Clinicopathologic and immunohistochemical study with
special emphasis on the alteration of cell cycle regulators., Histopathology 45; 29-38, 2004 (Corresponding), 10.1111/j.1365-2559.2004.01886.x, 45, 1, 29-38, 2004.01.
697. Shiratsuchi H, Hirakawa N, Saito T, Oda Y, Yamamoto H, Hachitanda Y, Tomita K, Komiyama S, Tsuneyoshi M, H-ras oncogene mutations in sarcomatous versus carcinomatous components of
aerodigestive spindle cell carcinoma., Oncology Report 11; 597-604, 2004, 2004.01.
698. Saito T, Oda Y, Kawaguchi K, Yamamoto H, Sugimachi K, Tateishi N, Tanaka K,Matsuda S, Iwamoto Y, Ladanyi M, Tsuneyoshi M:, E-cadherin mutation and Snail overexpression as alternative mechanisms of
E-cadherin inactivation in synovial sarcoma., Oncogene 23: 8629-8638, 2004, 10.1038/sj.onc.1207960, 23, 53, 8629-8638, 2004.01.
699. Yamamoto H, Oda Y, Saito T, Sakamoto A, Miyajima K, Tamiya S, Nakamori M, Tsuneyoshi M, p53 mutation and MDM2 amplification in inflammatory myofibroblastic tumors, Histopathology 42; 431-439, 2003, 10.1046/j.1365-2559.2003.01611.x, 42, 5, 431-439, 2003.01.
700. Naka T, Boltze C, Samii A, Herold C, Ostertag H, Iwamoto Y, Oda Y, Tsuneyoshi M, Kuester D, Roessner A:, Skull base and nonskullbase chordomas. Clinicopathologic and
immunohistochemical study with special reference to nuclear pleomorphism and
proliferative ability., Cancer 98; 1934-1941, 2003., 10.1002/cncr.11756, 98, 9, 1934-1941, 2003.01.
701. Adachi T, Oda Y, Sakamoto A, Terashi T, Tamiya S, Hachitanda Y, Tsuneyoshi M:, Prognostic factors in so-called malignant mesenchymona. A clinicopathologic
and immunohistochemical analysis of 12 cases., Oncology Rep 10; 803-811, 2003, 10, 4, 803-811, 2003.01.
702. Saito T, Oda Y, Kawaguchi K, Takahira T, Yamamoto H, Sakamoto A, Tamiya S, Iwamoto Y, Tsuneyoshi M, Possible association between tumor-suppressor gene mutations and hMSH2/hMLH1 inactivation in alveolar soft part sarcoma., Hum Pathol 34; 841-849, 2003., 10.1016/S0046-8177(03)00343-5, 34, 9, 841-849, 2003.01.
703. Saito T, Oda Y, Kawaguchi K, Takahira T, Yamamoto H, Tanaka K, Matsuda S, Sakamoto A, Tamiya S, Iwamoto Y, Tsuneyoshi M., PTEN/MMAC1 gene mutationis a rare event in soft tissue sarcomas without specific balanced translocations., Int J Cancer 104; 175-178, 2003, 10.1002/ijc.10918, 104, 2, 175-178, 2003.01.
704. Oda Y, Tamiya S, Tsuneyoshi M, Molecular genetic abnormalities and their usefulness for diagnosis and prediction of prognosis in soft-tissue sarcomas., Recent Res Devel Cancer 4; 305-315, 2002, 2003.01.
705. Kawaguchi K, Oda Y, Saito T, Yamamoto H, Tamiya S, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M, Mechanisms of inactivation of the p16 gene in leiomyosarcoma of soft tissue: The
absence of p16 expression correlates with the methylation status and poor
prognosis., J Pathol 201; 487-495, 2003., 10.1002/path.1419, 201, 3, 487-495, 2003.01.
706. Miyajima K, Oda Y, Tamiya S, Shimizu K, Hachitanda Y, Tsuneyoshi M., Cytogenetic and clinicopathologic analysis of soft-tissue leiomyosarcomas., Pathol Int 53; 163-168, 2003, 10.1046/j.1440-1827.2003.01449.x, 53, 3, 163-168, 2003.01.
707. Oda Y, Ohishi Y, Saito T, Hinoshita E, Uchiumi T, Kinukawa N, Iwamoto Y, Kohno K, Kuwano M, Tsuneyoshi M, Nuclear expression of Y box-binding protein-1 correlates with P-glycoprotein and
topoisomerase II-apha expression, and poor prognosis in synovial sarcoma., J Pathol 199; 251-258, 2003, 10.1002/path.1282, 199, 2, 251-258, 2003.01.
708. Oda Y, Takahira T, Kawaguchi K, Yamamoto H, Tamiya S, Matsuda S, Tanaka K, Kinukawa N, Iwamoto Y, Tsuneyoshi M:, Alterations of cell cycle regulators in myxofibrosarcoma. With special emphasis
on their prognostic implications., Human Pathol 34; 1035-1042, 2003, 2003.01.
709. Kuroiwa K, Kinoshita Y, Shiratsuchi H, Oshiro Y, Tamiya S, Oda Y, Naito S, Tsuneyoshi M, Renal cell carcinomas with rhabdoid features: an aggressive neoplasm., Histopathology 41; 538-548, 2002, 10.1046/j.1365-2559.2002.01427.x, 41, 6, 538-548, 2002.01.
710. Saito T, Oda Y, Kawaguchi K, Tanaka K, Matsuda S, Tamiya S, Iwamoto Y, Tsuneyoshi M, Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in soradic desmoid tumors: Real-time semiquantative assay by
TaqMan PCR., Lab Invest 82: 97-103, 2002, 82, 1, 97-103, 2002.01.
711. Kawaguchi K, Oda Y, Sakamoto A, Saito T, Tamiya S, Iwamoto Y, Tsuneyoshi M:, Molecular analysis of p53, MDM2 and H-ras genes in osteosarcoma and
malignant fibrous histiocytoma of bone in patients older than 40 years., Mod Pathol 15; 878-888, 2002, 10.1097/01.MP.0000024264.48690.EA, 15, 8, 878-888, 2002.01.
712. Saito T, Oda Y, Sakamoto A, Tamiya S, Iwamoto Y, Tsuneyoshi M, Matrix metalloproteinase-2 expression correlates with morphological and
immunohistochemical epithelial characters in synovial sarcoma., Histopathology 40: 279-285, 2002., 10.1046/j.1365-2559.2002.01345.x, 40, 3, 279-285, 2002.01.
713. Migita T, Oda Y, Naito S, Tsuneyoshi M, Low expression of p27 Cip/Kip1 is associated with tumor size and poor
prognosis in renal cell carcinoma., Cancer 94: 973-979, 2002., 10.1002/cncr.10338, 94, 4, 973-979, 2002.01.
714. Nishio J, Iwasaki H, Ishiguro M, Ohjimi Y, Fujita C, Isayama T, Naito M, Oda Y, Kaneko Y, Kikuchi M, Establishment of a new human synovial sarcoma cell line, FU-SY-1, that express
c-MET receptor and its ligand hepatocyte growth factor., Int J Oncol 21; 17-23, 2002., 21, 1, 17-23, 2002.01.
715. Miyajima K, Oda Y, Tamiya S, Oshiro Y, Kinukawa N, Masuda K, Tsuneyoshi M, Clinicopathologic prognostic factors in soft tissue leiomyosarcoma. A multivariate
analysis., Histopathology 40: 353-359, 2002, 2002.01.
716. Sakamoto A, Oda Y,Yamamoto H, Oshiro Y, Miyajima K, Itakura E, Tamiya S, Honda Y, Ishihara A, Iwamoto Y, Tsuneyoshi M, Calponin and h-caldesmon expression in atypical fibroxanthoma and superficial
leiomyosarcoma., Virchows Arch 440: 404-409, 2002., 10.1007/s004280100521, 440, 4, 404-409, 2002.01.
717. Sakamoto A, Oda Y, Adachi T, Saito T, Tamiya S, Iwamoto Y, Tsuneyoshi M:, Beta-catenin accumulation and gene mutation in exon 3 in dedifferentiated liposarcoma and malignant fibrous histiocytoma., Arch Pathol Lab Med 126; 1071-1078, 2002., 126, 9, 1071-1078, 2002.01.
718. Saito T, Oda Y, Sakamoto A, Kawaguchi K, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M, APC mutations in synovial sarcoma, J Pathol 196: 445-449, 2002, 10.1002/path.1066, 196, 4, 445-449, 2002.01.
719. Oda Y, Tamiya S, Oshiro Y, Hachitanda Y, Kinukawa N, Iwamoto Y, Tsuneyoshi M, Reassessment of malignant fibrous histiocytoma of soft parts and its
clinicopathologic prognostic factors., Pathol Int 52; 595-606, 2002, 2002.01.
720. Shiratsuchi H, Saito T, Sakamoto A, Itakura E, Tamiya S, Oshiro Y, Oda Y, Toh S, Komiyama S, Tsuneyoshi M:, Mutation analysis of human cytokeratin 8 (KRT 8) in malignant rhabdoid tumor: A
possible association with intracytoplasmic inclusion body formation., Mod Pathol 15: 146-153, 2002., 10.1038/modpathol.3880506, 15, 2, 146-153, 2002.01.
721. Ohishi Y, Oda Y, Uchiumi T, Kobayashi H, Hirakawa T, Miyamoto S, Kinukawa N, Nakano H, Kuwano M, Tsuneyoshi M:, ATP-binding casstte superfamily transporter gene expression in human ovarian
carcinoma, Clin Cancer Res 8; 3767-3775, 2002, 8, 12, 3767-3775, 2002.01.
722. Saito T, Oda Y, Tanaka K, Matsuda S, Tamiya S, Iwamoto Y, Tsuneyoshi M, b-catenin nuclear expression correlates with cyclin D1 overexpression in
sporadic desmoid tumors., J Pathol 195; 222-228, 2001, 10.1002/path.942, 195, 2, 222-228, 2001.01.
723. Migita T, Oda Y, Naito S, Kuwano M, Tsuneyoshi M, The accumulation of angiostatin-like fragments in human prostate carcinoma, Clin Cancer Res 7: 2750-2756, 2001, 7, 9, 2750-2756, 2001.01.
724. Itakura E, Tamiya S, Morita K, Shiratsuchi H, Kinoshita Y, Oshiro Y, Oda Y, Ohta S, Furue M, Tsuneyoshi M, Subcellular distribution of cytokeratin and vimentin in malignant rhabdoid
tumor: Three-dimensional imaging with confocal laser scanning microscopy and
double immunofluorescence., Mod Pathol 14: 854-861, 2001, 10.1038/modpathol.3880401, 14, 9, 854-861, 2001.01.
725. Oda Y, Sakamoto A, Saito T, Matsuda S, Tanaka K, Iwamoto Y, Tsuneyoshi M:, Secondary malignant giant-cell tumor of bone. Molecular abnormalities of p53
and H-ras gene correlated with malignant transformation ., Histopathology 39: 629-637, 2001, 10.1046/j.1365-2559.2001.01275.x, 39, 6, 629-637, 2001.01.
726. Miyajima K, Tamiya S, Oda Y, Adachi T, Konomoto T, Toyoshiba H, Masuda K, Tsuneyoshi M, Relative quantitation of p53 and MDM2 gene expression in leiomyosarcoma;
Real-time semi-quantative RT-PCR., Cancer Letters 164; 177-188, 2001, 10.1016/S0304-3835(00)00607-8, 164, 2, 177-188, 2001.01.
727. Kinoshita Y, Shiratsuchi H, Tamiya S, Oshiro Y, Oda Y, Suita S, Tsuneyoshi M:, Mutations of p53 gene in malignant rhabdoid tumors of soft tissue and kidney:
Immunohistochemical and DNA direct sequence analysis., J Cancer Res Clin Oncol 127: 351-358; 2001, 10.1007/s004320000217, 127, 6, 351-358, 2001.01.
728. Watanabe T, Oda Y, Tamiya S, Kinukawa N, Masuda K, Tsuneyoshi M, Malignant peripheral nerve sheath tumors: high Ki67 labelling index is the
significant prognostic indicator., Histopathology 39; 187-197, 2001, 10.1046/j.1365-2559.2001.01176.x, 39, 2, 187-197, 2001.01.
729. Kawauchi S, Goto Y, Liu X-P, Furuya T, Oga A, Oda Y, Tsuneyoshi M, Ihara K, Sasaki K, Low expression of p27Kip1, a cyclin-dependent kinase inhibitor, is a marker of poor prognosis in synovial sarcoma, Cancer 91; 1005-1012, 2001, 10.1002/1097-0142(20010301)91:5<1005::AID-CNCR1091>3.0.CO;2-O, 91, 5, 1005-1012, 2001.01.
730. Adachi T, Oda Y, Sakamoto A, Saito T, Tamiya S, Masuda K, Tsuneyoshi M, Immunoreactivities of p53, MDM2 and p21/WAF1 in dedifferentiated liposarcoma.
Special emphasis on the distinct immunophenotype of the well-differentiated
component., Int J Surg Pathol 9; 99-109, 2001, 10.1177/106689690100900203, 9, 2, 99-109, 2001.01.
731. Naka T, Oda Y, Iwamoto Y, Shinohara N, Chuman H, Fukui M, Tsuneyoshi M, Immunohistochemical analysis of E-cadherin, alpha-, beta-, gamma-cetenins,
and neural cell adhesion molecule (NCAM) in chordoma., J Clin Pathol 54; 945-950, 2001, 54, 12, 945-950, 2001.01.
732. Sakamoto A, Oda Y, Itakura E, Oshiro Y, Nikaido O, Iwamoto Y, Tsuneyoshi M, Immunoexpression of ultraviolet photoproducts and p53 mutation analysis in
atypical fibroxanthoma and superficial malignant fibrous histiocytoma, Mod Pathol 14; 581-588, 2001, 10.1038/modpathol.3880354, 14, 6, 581-588, 2001.01.
733. Sakamoto A, Oda Y, Oshiro Y, Tamiya S, Iwamoto Y, Tsuneyoshi M:, Immunoexpression of neurofibromin, S-100 protein and Leu-7 and mutation
analysis of the NF1 gene at codon 1423 in osteofibrous dysplasia, Hum Pathol 32: 1245-1251, 2001, 10.1053/hupa.2001.28954, 32, 11, 1245-1251, 2001.01.
734. Sakamoto A, Oda Y, Adachi T, Tamiya S, Matsuda S, Tanaka K, Iwamoto Y, Tsuneyoshi M, H-ras oncogene mutations in dedifferentiated liposarcomas. polymerase chain
reaction-restriction fragment length polymorphism analysis of
paraffin-embedded tissues., Am J Clin Pathol 115; 235-242, 2001, 115, 2, 235-242, 2001.01.
735. Sakamoto A, Oda Y, Adachi T, Oshiro Y, Tamiya S, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M, H-ras oncogene mutation in dedifferentiated chondrosarcoma: Polymerase
chain reaction-restriction fragment length polymorphism analysis., Mod Pathol 14; 343-349, 2001., 10.1038/modpathol.3880313, 14, 4, 343-349, 2001.01.
736. Sakamoto A, Oda Y, Itakura E, Oshiro Y, Tamiya S, Honda Y, Ishihara A, Iwamoto Y, Tsuneyoshi M, H-, K- and N-ras mutation in atypical fibroxanthoma and malignant fibrous
histiocytoma., Hum Pathol 32: 1225-1231, 2001, 10.1053/hupa.2001.28953, 32, 11, 1225-1231, 2001.01.
737. Kinoshita K, Tamiya S, Oda Y, Hirano K, Mimori K, Inoue H, Ohta S, Suita S, Tsuneyoshi M, Establishment and characterization of malignant rhabdoid tumor of the kidney:Immunohistochemical and cytogenetical analysis., Oncology Reports 8: 43-48; 2001, 8, 1, 43-48, 2001.01.
738. Saito T, Oda Y, Sugimachi K, Kawaguchi K, Tamiya S, Tanaka K, Matsuda S, Sakamoto A, Iwamoto Y, Tsuneyoshi M:, E-Cadherin gene mutations frequently occur in synovial sarcoma as a
determinant of histological features ., Am J Pathol 159: 2117-2124, 2001, 10.1016/S0002-9440(10)63063-5, 159, 6, 2117-2124, 2001.01.
739. Shiratsuchi H, Oshiro Y, Itakura E, Kinoshita Y, Tamiya S, Oda Y, Ohta S, Komiyama S, Tsuneyoshi M:, Cytokeratin subunits of inclusion bodies in rhabdoid cells: Immunohistochemical
and clinicopathological study of malignant rhabdoid tumor and epithelioid sarcoma., Int J Surg Pathol 9 (1): 37-48, 2001, 10.1177/106689690100900107, 9, 1, 37-48, 2001.01.
740. Oda Y, Miyajima K, Kawaguchi K, Tamiya S, Oshiro Y, Hachitanda Y, Oya M, Iwamoto Y, Tsuneyoshi M, Pleomorphic leiomyosarcoma: Clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and
malignant fibrous histiocytoma., Am J Surg Pathol 25; 1030-1038, 2001, 10.1097/00000478-200108000-00007, 25, 8, 1030-1038, 2001.01.
741. Watanabe T, Oda Y, Tamiya S, Masuda K, Tsuneyoshi M:, Malignant peripheral nerve sheath tumor arising within neurofibroma.
An immunohistochemical analysis in the comparison between benign and
malignant components., J Clin Pathol 54; 631-636, 2001., 10.1136/jcp.54.8.631, 54, 8, 631-636, 2001.01.
742. Saito T, Oda Y, Oshiro Y, Shitatsuchi H, Itakura E, Kinoshita Y, Tamiya S, Iwamoto Y, Tsuneyoshi M:, Expression of intercellular adhesion molecules in epithelioid sarcoma and
malignant rhabdoid tumor., Pathol Int 51: 532-542, 2001, 10.1046/j.1440-1827.2001.01232.x, 51, 7, 532-542, 2001.01.
743. Oshiro Y, Shiratsuchi H, Oda Y, Toyoshima S, Tsuneyoshi M:, Rhabdoid features in leiomyosarcoma of soft tissue: with special reference to its aggressive behabior., Mod Pathol 13: 1211-1218, 2000., 10.1038/modpathol.3880225, 13, 11, 1211-1218, 2000.01.
744. Saito T, Oda Y, Sakamoto A, Tamiya S, Kinukawa N, Hayashi K, Iwamoto Y,, Prognostic value of the preserved expressions of adhesion molecules
(E-cadherin and catenin families) and beta-catenin mutation in synovial sarcoma., J Pathol 192: 342-350, 2000., 10.1002/1096-9896(2000)9999:9999<::AID-PATH705>3.0.CO;2-R, 192, 3, 342-350, 2000.01.
745. Kawauchi S, Fukuda T, Oda Y, Saito T, Oga A, Takeshita M, Yokoyama K, Chuman H, Iwamoto Y, Sasaki K, Tsuneyoshi M:, Prognostic significance of apoptosis in synovial sarcoma: Correlation with
clinicopathologic parameters, cell proliferative activity and expression of
apoptosis-related proteins., Mod Pathol 13: 755-765, 2000, 10.1038/modpathol.3880131, 13, 7, 755-765, 2000.01.
746. Watanabe T, Sakamoto A, Tamiya S, Oda Y, Masuda K, Tsuneyoshi M, H-ras-1 point mutation in malignant peripheral nerve sheath tumors.
Polymerase chain reaction-restriction fragment length polymorphism analysis
and direct sequencing from paraffin embedded tissues., International Journal of Molecular Medicine 5: 605-608, 2000, 5, 6, 605-608, 2000.01.
747. Oshiro Y, Shiratsuchi H, Tamiya S, Oda Y, Toyoshima S, Tsuneyoshi M:, Extraskeletal myxoid chondrosarcoma with rhabdoid feature: a special reference
to its aggressive behavior., Int J Surg Pathol 8: 145-152, 2000, 10.1177/106689690000800209, 8, 2, 145-152, 2000.01.
748. Oda Y, Sakamoto A, Saito T, Iwamoto Y, Kinukawa N, Tsuneyoshi M, Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor
c-MET correlates with poor prognosis in synovial sarcoma., Hum Pathol 31: 185-192, 2000, 10.1016/S0046-8177(00)80218-X, 31, 2, 185-192, 2000.01.
749. Shinokuma A, Hirakawa N, Tamiya S, Oda Y, Komiyama S, Tsuneyoshi M, Evaluation of Epstein-Barr virus infection in sinonasal small round cell tumors., J Cancer Res Clin Oncol 126: 12-18, 2000, 10.1007/PL00008459, 126, 1, 12-18, 2000.01.
750. Oda Y, Matsumoto Y, Harimaya K, Iwamoto Y, Tsuneyoshi M, Establishment of new multidrug-resistant human osteosarcoma cell lines, Oncology Reports 7: 859-866, 2000., 7, 4, 859-866, 2000.01.
751. Oda Y, Naka T, Takeshita M, Iwamoto Y, Tsuneyoshi M:, Comparison of histologic changes and changes in nm23 and c-MET expression
between primary and metastatic sites in osteosarcoma. A clinicopathologic and
immunohistochemical study., Hum Pathol 31: 709-716, 2000, 10.1053/hupa.2000.8230, 31, 6, 709-716, 2000.01.
752. Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M, A comparative study of fibrous dysplasia and osteofibrous dysplasia with
regard to Gs-alpha mutation at Arg201 codon: polymerase chain reaction-
restriction fragment length polymorphism analysis of paraffin-embedded tissues, J Mol Diag 2: 67-72, 2000., 10.1016/S1525-1578(10)60618-6, 2, 2, 67-72, 2000.01.
753. Oda Y, Sakamoto A, Saito T, Kawauchi S, Iwamoto Y, Tsuneyoshi M:, Molecular abnormalities of p53, MDM2 and H-ras in synovial sarcoma., Mod Pathol 13: 994-1004, 2000., 10.1038/modpathol.3880180, 13, 9, 994-1004, 2000.01.
754. Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M, Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in human
cartilaginous tumors with special emphasis on mesenchymal and
dedifferentiated chondrosarcoma., J Cancer Res Clin Oncol 125; 541-548, 1999, 10.1007/s004320050314, 125, 10, 541-548, 1999.01.
755. Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M, A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard
to expressions of c-fos and c-jun products and bone matrix proteins. A
clinicopathologic review and immunohistochemical study of c-fos, c-jun, type I
collagen, oseonectin, osteopontin, and osteocalcin., Hum Pathol 30: 1418-1426, 1999, 1999.01.
756. Radig K, Schneider-Stock R, Rose I, Mittler U, Oda Y, Roessner A:, p53 and ras mutations in Ewing's sarcoma., Path Res Pract 194(3); 157-162, 1998, 194, 3, 157-162, 1998.01.
757. Schneider-Stock R, Epplen C, Radig K, Oda Y, Dralle H, Hoang-Vu C, Epplen JT, Roessner A, On teromere shortening in soft-tissue tumors, J Cancer Res Clin Oncol 124: 165-171, 1998, 10.1007/s004320050150, 124, 3-4, 165-171, 124: 165-171, 1998, 1998.01.
758. Oda Y, Miura H, Tsuneyoshi M, Iwamoto Y, Giant cell tumor of bone. Oncologic and functional results of long-term follow-up, Jpn J Clin Oncol 28: 323-328, 1998, 10.1093/jjco/28.5.323, 28, 5, 323-328, 1998.01.
759. Oda Y, Sakamoto A, Shinohara N, Ohga T, Uchiumi T, Kohno K, Tsuneyoshi M, Kuwano M, Iwamoto Y, Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in
human osteosarcoma., Clin Cancer Res 4: 2273-2277, 1998, 4, 9, 2273-2277, 1998.01.
760. Kenichi Kohashi, Hidetaka Yamamoto, Reiko Kumagai, Yuichi Yamada, Yuka Hotokebuchi, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda, Differential microRNA expression profiles between malignant rhabdoid tumor and epithelioid sarcoma: miR193a-5p is suggested to down regulate SMARCB1/INI1 mRNA expression

, Mod Pathol, 2014 Jun;27(6):832-9, 10.1038/modpathol.2013.213., 27, 6, 832-829.
761. Shinichi Aishima, Yuki Tanaka, Yuichiro Kubo, Yohei Mano, Yo-ichi Yamashita, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda, Distinct clinicopathological features of combined hepatocellular-chlangiocarcinoma: A proposal for classification by non-hepatocellular component., Histopathology, in press .
762. Yuichi Hisamatsu, Eriko Kitao Tokunaga, Nami Yamashita, Akiyoshi Sayuri, Satoko Okada, Yuichiro Nakashima, Kenji Taketani, Shinichi Aishima, Yoshinao Oda, Masaru Morita, Yoshihiko Maehara, Impact of GATA-3 and FOXA1 expression in patients with hormone receptor-positive/HER2-negative breast cancer., Breast Cancer. 2014 Jan 11, in press .
763. Ohtsuka Takao, Koji Tamura, Noboru Ideno, Teppei Aso, Yosuke Nagayoshi, Hiroshi Kono, JUNJI UEDA, Shunichi Takahata, Akira Aso, Hisato Igarashi, Tetsuhide Ito, Yasuhiro Ushijima, Fumihiko Ookubo, Yoshinao Oda, Mizumoto Kazuhiro, Masao Tanaka, The role of ERCP in the era of EUS-FNA for preoperative cytological confirmation of resectable pancreatic ductal adenocarcinoma., Surg Today, in press. 2014 Feb 5. .
764. Yuichiroh Umemoto, Shinji Okano, Yoshihiro Matsumoto, Hidekazu Nakagawara, Rumi Matono, Shohei Yoshiya, Yo-ichi Yamashita, Tomoharu Yoshizumi, ikegami Toru, Yuji Soejima, Mamoru Harada, Shinichi Aishima, Yoshinao Oda, Ken Shirabe, Yoshihiko Maehara, Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy., Gastroenterol. 2014 Feb 8, in press .
765. Y Oda, Shinichi Aishima, K Morimatsu, Koji Shindo, Minoru Fujino, Yusuke Mizuuchi, Masami Hattori, Tetsuyuki Miyazaki, Masao Tanaka, Yoshinao Oda, Pancreatic intraepithelial neoplasia in the background of invasive ductal carcinoma of pancreas as a prognostic factor.
, Histopathology, in press .
766. Harimoto Norifumi, ikegami Toru, H Nakagawara, Y Yamashita, T Yoshizumi, Hideaki Uchiyama, Yuji Soejima, T Ikeda, Ken Shirabe, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara, Chronic immune-mediated reaction syndrome as the cause of late graft mortality in living donor liver transplantation for primary biliary cirrhosis., Transplantation Proceedings, in press .
767. Yuichiro Kubo, Shinichi Aishima, Yuki Tanaka, Koji Shindo, Yusuke Mizuuchi, Koichiro Abe, Ken Shirabe, Yoshihiko Maehara, Hiroshi Handa, Yoshinao Oda, Different expression of Glucose transporters in the progression of intrahepatic cholangiocarcinoma. , Hum Pathol, in press (corresponding) .
768. Yohei Mano, Shinichi Aishima, Yuichiro Kubo, Yuki Tanaka, T Motomura, T Toshima, Ken Shirabe, K Abe, Yoshihiko Maehara, Yoshinao Oda, Correlation between Biological Marker Expression and Fluorine-18 Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma Measured by Positron Emission Tomography., Am J Clin Pathol, in press (corresponding) .
769. K Kataoka, K Tanaka, Yoshinao Oda, Yukihide Iwamoto, A randomized phase II/III trial of perioperative chemotherapy with adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-grade soft tissue sarcoma: Japan Clinical Oncology Group study JCOG1306., Jpn J Clin Oncol, in press .
770. Kina Miyoshi, Kenichi Kohashi, F Fushimi, Hidetaka Yamamoto, T Taguchi, Yukihide Iwamoto, Yoshinao Oda, Close correlation between CXCR4 and VEGF expression and frequent CXCR7 expression in rhabdomyosarcoma. , Hum Pathol, in press (corresponding) .
771. Shinichi Aishima, Yuki Tanaka, Yuichiro Kubo, Yohei Mano, Yo-ichi Yamashita, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda, Distinct clinicopathological features of combined hepatocellular-chlangiocarcinoma: A proposal for classification by non-hepatocellular component.

, Histopathology, in press.
772. Hisamatsu Y, Eriko Kitao Tokunaga, Yamashita N, Akiyoshi S, Yasuharu Nakashima, Shinichi Aishima, Yoshinao Oda, Morita M, Yoshihiko Maehara, Impact of GATA-3 and FOXA1 expression in patients with hormone receptor-positive/HER2-negative breast cancer., Breast Cancer. 2014 Jan 11, in press.
773. Nakamura M, Koji Shindo, Ideno N, JUNJI UEDA, Shunichi Takahata, Nakashima H, Ohtsuka Takao, Shimizu S, Yoshinao Oda, Masao Tanaka, Prediction of Pancreatic Fistula by Preoperatively Assessable Factors; Retrospective Review of Unified Operations by Single Surgeon., Hepato-Gastroenterology, in press.
774. Yoshida R, Morita M, Shoji F, Nakashima Y, Miura N, Yoshinaga K, Koga T, Tokunaga E, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Yoshihiko Maehara, Clinical Significance of SIP1 and E-cadherin in Patients with Esophageal Squamous Cell Carcinoma., Ann Surg Oncol, in press 2015 Jan 7..
775. Kunio Iura, Kenichi Kohashi, Akira Maekawa, Yuichi Yamada, Yuka Hotokebuchi, Hidetaka Yamamoto, Yukihide Iwamoto, Yoshinao Oda, Cancer-testis antigen PRAME and NY-ESO-1 correlates with tumor grade and poor prognosis in myxoid/round cell liposarcoma., J Pathol, Clin Pract, in press (corresponding).
776. Yoshihiro Ohishi, Hiroko Imamura, Murasaki Aman, Takeuchi T, Kaai Shida, Kurihara S, Tsunehisa Kaku, Kobayashi H, Yoshinao Oda, Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma ?, Int J Gynecol Pathol, in press.
777. Iwama E, Takeyama K, Harada T, Okamoto I, Eishi Baba, Yoshinao Oda, Yoichi Nakanishi, Highly sensitive and quantitative detection of EGFR T790M mutations in tumor samples by Nanofluidic Digital PCR., Oncotarget, in press.
778. Iwama E, Takeyama K, Harada T, Okamoto I, Eishi Baba, Yoshinao Oda, Yoichi Nakanishi, Highly sensitive and quantitative detection of EGFR T790M mutations in tumor samples by Nanofluidic Digital PCR., Oncotarget, in press.
779. Ikegami K, Nakamura S, motohiro esaki, Yanai S, Minako Hirahashi, Yoshinao Oda, Takeshita M, Matsumoto T, Takanari Kitazono, Prognostic value of chromosomal translocations in small bowel diffuse large B-cell lymphoma..
780. Bekki Y, Kimura Y, Morita M, Yoko Zaitsu, Hiroshi Saeki, Okomoto T, Eiji Oki, Baba S, Yoshinao Oda, Yoshihiko Maehara, Esophageal cancer associated with bilateral hilar lymphadenopathy caused by sarcoid‑like reactions: a report of two cases., Esophagus, in press.
781. Okano S, Takahara M, Suzuki H, Fujii H, Ken Shirabe, Yoshinao Oda, Yoshihiko Maehara, Masutaka Furue, Cutaneous epithelioid angiomatous nodule in a patient with a history of multiple pyogenic granuloma., Eur J Dermatol, in press.
782. Abe I, Kaeasaki S, Sakamoto S, Marsuda Y, Nakashima T, Hidetaka Yamamoto, Kawate H, Ohnaka K, Nakashima H, Kobayashi K, Yoshinao Oda, Ryoichi Takayanagi, Complete remission of anaplastic thyroid carcinoma after concomitant treatment with docetaxel and radiotherapy. , Case report in Endocrinology, in press.
783. Nakahara T, Yuchi Yamada, Itho E, Makiko Kido-Nakahara, Yoshinao Oda, Kiryu H, Masutaka Furue, A case of ossifying epithelioid hemangioendothelioma on the forearm , Journal of Dermatology, in press .
784. Ito, Takamichi, Kenichi Kohashi, Yamada, Yuich, Iwasaki, Takeshi, Maekawa, Akira, Kuda, Masaaki, Hoshina, Daichi, Abe, Riichiro, Furue, Masutaka, Yoshinao Oda, Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma, JOURNAL OF CANCER, 10.7150/jca.14461, 7, 7, 823-830.
785. Sugimoto, Masaaki, Kohashi Kenichi, Itsumi, Momoe, Shiota, Masaki, Abe, Tatsuro, Yamada, Yuichi, Kuroiwa, Kentaro, Naito, Seiji, Oda Yoshinao, Epithelial to Mesenchymal Transition in Clear Cell Renal Cell Carcinoma with Rhabdoid Features, PATHOBIOLOGY, 10.1159/000445752, 83, 6, 277-286.
786. Otsu, Hajime, Iimori, Makoto, Ando, Koji, Saeki, Hiroshi, Aishima, Shinichi, Oda, Yoshinao, Morita, Masaru, Matsuo, Keitaro, Kitao, Hiroyuki, Oki, Eiji, Maehara, Yoshihiko, Gastric Cancer Patients with High PLK1 Expression and DNA Aneuploidy Correlate with Poor Prognosis, ONCOLOGY, 10.1159/000445952, 91, 1, 31-40.
787. Bekki, Hirofumi, Kohashi, Kenichi, Yamada, Yuichi, Iura, Kunio, Ishii, Takeaki, Maekawa, Akira, Otsuka, Hiroshi, Yamamoto H, Hakozaki, Michiyuki, Nabeshima, Kazuki, Iwamoto, Yukihide, Oda, Y, Phosphorylation of STAT3 in Undifferentiated Pleomorphic Sarcoma Is Correlated with a Favorable Prognosis, PATHOBIOLOGY, 10.1159/000448524, 84, 3, 161-169.