2024/07/28 更新

お知らせ

 

写真a

モウリ タロウ
毛利 太郎
MORI TARO
所属
医学研究院 基礎医学部門 助教
医学部 医学科(併任)
医学系学府 医療経営・管理学専攻(併任)
職名
助教
連絡先
メールアドレス
電話番号
0926426072
外部リンク

学位

  • 2023年3月 九州大学, 博士 (医学)

研究テーマ・研究キーワード

  • 研究テーマ: 骨軟部腫瘍における治療標的・予後因子の解明

    研究キーワード: 骨軟部腫瘍, 病理

    研究期間: 2023年4月 - 2027年3月

論文

  • DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases. 査読 国際誌

    Mori T, Iwasaki T, Sonoda H, Kawaguchi K, Tomonaga T, Furukawa H, Sato C, Shiraishi S, Taguchi K, Tamiya S, Yoneda R, Oshiro Y, Matsunobu T, Abe C, Kuboyama Y, Ueki N, Kohashi K, Yamamoto H, Nakashima Y, Oda Y.

    Human Pathology   145   56 - 62   2024年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5') and centromeric (3') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category.

    DOI: 10.1016/j.humpath.2024.02.007.

  • Clinicopathological and histopathological review of dedifferentiated liposarcoma: a comprehensive study of 123 primary tumours. 査読 国際誌

    Mori T, Yamada Y, Kinoshita I, Kohashi K, Yamamoto H, Ito Y, Susuki Y, Kawaguchi K, Nakashima Y, Oda Y

    Histopathology   80 ( 3 )   538 - 557   2022年2月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aims: Dedifferentiated liposarcoma (DDLS) has varying histopathological features, but their significance for the biological behaviour of this disease has not been fully clarified. The aim of this study was to elucidate the prognostic factors for DDLS by clinicopathologically reviewing a large case series.
    Methods and results: We clinicopathologically reviewed 123 cases of primary de-novo DDLS without preoperative treatment, including 81 in the internal trunk (internal DDLS) and 42 in peripheral sites (peripheral DDLS). Univariate and multivariate analyses of their features were also performed for all cases, the internal DDLS group, and the peripheral DDLS group. The results showed that, in all three groups, distant metastasis was significantly associated with shorter overall survival (OS) (univariate analysis, P < 0.0001, P = 0.0011, and P = 0.0101, respectively), whereas local recurrence showed no significant effect on prognosis. Histopathologically, a high mitotic count and the presence of round tumour cells were significantly associated with shorter OS in multivariate analysis of the internal DDLS group [respectively: P = 0.0022, hazard ratio (HR) 4.39, 95% confidence interval (CI) 1.71-11.28; and P = 0.0014, HR 7.19, 95% CI 2.14-24.16]. In the peripheral DDLS group, necrosis and high-grade histological components were significantly associated with shorter OS (univariate analysis, P = 0.0068 and P = 0.0174, respectively).
    Conclusions: The presence of round tumour cells may be one of the histological factors associated with a worse prognosis of DDLS patients, as previous studies indicated. This study also suggests that distant metastasis may be predictive of prognosis for both internal and peripheral DDLS, rather than local recurrence.

    DOI: 10.1111/his.14588.

  • Nuclear morphological atypia in biopsy accurately reflects the prognosis of myxoid liposarcoma. 査読 国際誌

    Kawaguchi K, Kohashi K, Iwasaki T, Mori T, Furukawa H, Sato C, Sonoda H, Shiraishi S, Endo M, Nakashima Y, Oda Y.

    Virchows Archiv   2024年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Currently, it is difficult to predict the prognosis of myxoid liposarcoma (MLS) in biopsy specimens. In this study, we determined whether nuclear morphology may be used to predict the prognosis of MLS in primary biopsy specimens. Two pathologists evaluated nuclear morphology using the modified WHO/ISUP and Fuhrman grades. Survival analyses were performed by grouping nuclear high- and low-grades. We examined 53 MLS cases, which included 29 (54.7%) male and 24 (45.3%) female patients with a median age of 46 years (interquartile range, 37 - 60). In total, 7 (13.2%) and 16 (30.2%) cases were assigned to the high nuclear grade group based on the modified WHO/ISUP and Fuhrman gradings, respectively. Survival analyses revealed a significantly worse disease-free survival in the high-grade group (hazard ratio (HR), 7.51; 95% confidence interval (CI), 2.67-21.1, p < 0.001 by the modified WHO/ISUP grading; HR, 4.45; 95% CI, 1.63-12.1, p = 0.001 by the modified Fuhrman grading). Moreover, the modified WHO/ISUP grade showed a significantly worse overall survival in the high-grade group (HR, 4.39; 95% CI, 1.04-18.6, p = 0.028), and the modified Fuhrman grade exhibited a similar, but not significant, trend. Our results indicate that nuclear morphology grading is a good predictor of patient prognosis at the time of biopsy in MLS. Even when cell density is sparse, treatment strategies should be carefully considered when individual tumor cells exhibit atypical nuclei.

    DOI: 10.1007/s00428-024-03796-7

  • Prognostic implications of the immunohistochemical expression of perilipin 1 and adipophilin in high-grade liposarcoma 査読 国際誌

    Kawaguchi K, Kohashi K, Mori T, Yamamoto H, Iwasaki T, Kinoshita I, Susuki Y, Furukawa H, Endo M, Matsumoto Y, Nakashima Y, Oda Y

    Journal of Clinical Pathology   2023年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aims: Liposarcoma is a malignant soft tissue tumour with adipocytic differentiation. Dedifferentiated liposarcoma (DDLS) and myxoid liposarcoma (MLS) are classified as high-grade liposarcomas. Lipid droplet-associated protein (also known as perilipin 1 (PLIN1)) is the predominant perilipin and has utility as a specific marker of adipogenic differentiation. Adipose differentiation-related protein (also known as adipophilin (ADRP)) is ubiquitously expressed in a range of tissues. High ADRP expression is reportedly a poor prognostic factor in several cancer types. However, no previous studies have examined the association between PLIN1 or ADRP expression and prognosis in sarcoma. This study therefore aimed to evaluate the association between PLIN1 or ADRP expression and prognosis in liposarcoma.
    Methods: In total, 97 primary resection specimens (53 MLS and 44 DDLS) were examined in this study. PLIN1 and ADRP expression was evaluated by immunohistochemistry. Survival analyses were performed for MLS and DDLS.
    Results: Of the 53 MLS specimens, 15 (28.3%) exhibited high PLIN1 expression. PLIN1 expression was not observed in DDLS specimens. High PLIN1 expression was significantly associated with increased disease-free survival (DFS) among patients with MLS (p=0.045). Distinct ADRP expression was observed in 13 of 53 (24.5%) MLS specimens and 5 of 44 (11.4%) DDLS specimens. High ADRP expression was associated with shorter overall survival (OS) in MLS (p=0.042) and DFS and shorter OS in DDLS (p=0.024 and p<0.001, respectively).
    Conclusions: PLIN1 and ADRP expression is associated with poor prognosis in high-grade liposarcoma.

    DOI: 10.1136/jcp-2023-208814.

  • Myxoid type and non-myxoid type of intimal sarcoma in large vessels and heart: review of histological and genetic profiles of 20 cases 査読 国際誌

    Yamada Y, Kinoshita I, Miyazaki Y, Tateishi Y, Kuboyama Y, Iwasaki T, Kohashi K, Yamamoto H, Ishihara S, Toda Y, Ito Y, Susuki Y, Kawaguchi K, Hashisako M, Yamada-Nozaki Y, Kiyozawa D, Mori T, Yamamoto T, Tsuchihashi K, Kuriwaki K, Mukai M, Kawai M, Suzuki K, Nishimura H, Bando K, Masumoto J, Fukushima M, Motoshita J, Mori H, Shiose A, Oda Y

    Virchows Archiv   480 ( 4 )   919 - 925   2022年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Intimal sarcoma is one of the most common and well-known primary malignant neoplasms of the aorta and heart. The authors reviewed cases of intimal sarcoma from histological, immunohistochemical and genetic perspectives. Twenty cases of intimal sarcoma were retrieved. Immunohistochemistry and FISH of MDM2 and PDGFRA genes were performed. All 20 tumours were composed of spindle-shaped, stellate, oval or polygonal tumour cells with irregular hyperchromatic nuclei arranged in a haphazard pattern, accompanied by nuclear pleomorphism and frequent mitotic figures. Other histological findings were as follows: abnormal mitosis in 10 cases (50%), necrosis in 15 cases (75%), myxoid stroma in 12 cases (60%), cartilaginous formation in 1 case (5%), haemorrhage in 12 cases (60%) and fibrinous deposition in 14 cases (70%). The tumours were positive for MDM2 in 16 cases (80%), ERG in 4 cases (20%), alpha-smooth muscle actin in 6 cases (30%), desmin in 5 cases (25%) and AE1/AE3 in 4 cases (20%). Immunohistochemical positivity was focal in each case. Loss of H3K27me3 expression was noted in 2 cases (10%). MDM2 and PDGFRA gene amplifications were detected in 11 cases (55%) and 1 case (5%), respectively. Fisher's exact test revealed a significant correlation between MDM2 gene amplification and myxoid stroma (p = 0.0194). No parameters showed any association with the anatomical location of the tumours. It was suggested that myxoid histology of intimal sarcoma may be associated with MDM2 gene amplification and that intimal sarcoma may be divided into myxoid and non-myxoid types.

    DOI: 10.1007/s00428-022-03293-9.

  • Clinicopathological and prognostic significance of H3K27 methylation status in malignant peripheral nerve sheath tumor: correlation with skeletal muscle differentiation. 査読 国際誌

    Ito Y, Kohashi K, Endo M, Yoshimoto M, Ishihara S, Toda Y, Susuki Y, Kawaguchi K, Furukawa H, Tateishi Y, Yamada Y, Kinoshita I, Mori T, Yamamoto H, Nakashima Y, Oda Y

    Virchows Archiv   479 ( 6 )   1233 - 1244   2021年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Malignant peripheral nerve sheath tumor (MPNST) is a very aggressive peripheral nerve sheath-derived sarcoma, which is one of the most difficult tumors to diagnose due to its wide spectrum of histological findings and lack of specific immunohistochemical markers. Recently, it has been reported that losses of expression of H3K27me3 and H3K27me2 caused by PRC2 dysfunction may be useful diagnostic markers for MPNST, but there is no consensus on their clinicopathological significance. Here, we investigated the relationship between loss of H3K27 methylation and various parameters and clarified the clinicopathological significance of such loss. We analyzed the clinicopathological and immunohistochemical features in 84 MPNST cases. Complete losses of H3K27me3 and H3K27me2 were observed in 37 (44%) and 29 (35%) cases, respectively. Losses of H3K27me3 and H3K27me2 were significantly correlated with myogenic immunopositivity (H3K27me3 vs. desmin, P = 0.0051; H3K27me3 vs. myogenin, P = 0.0009; H3K27me2 vs. myogenin, P = 0.042). Meanwhile, there were significant correlations between preservation of immunohistochemical neurogenic markers and intact H3K27me3 and H3K27me2 (H3K27me3 vs. S-100 protein, P = 0.0019; H3K27me3 vs. SOX10, P = 0.014; H3K27me2 vs. S-100 protein, P = 0.0011; H3K27me2 vs. SOX10, P = 0.0087). In multivariate analysis, local recurrence, distant metastasis, high FNCLCC grade, and loss of SOX10 expression were independent prognostic factors for overall survival. H3K27me3 and H3K27me2 expression was retained in all 26 cases of rhabdomyosarcoma non-alveolar subtype. In conclusion, we suggest that H3K27me3 and H3K27me2 immunonegativity is useful but not definitive for diagnosing MPNST. Complete loss of H3K27 methylation may be involved in aggressive transdifferentiation from neural differentiation to skeletal muscle differentiation in MPNST.

    DOI: 10.1007/s00428-021-03189-0.

  • Prognostic implication of desmoplastic stroma in synovial sarcoma: A histological review. 招待 査読 国際誌

    Toda Y, Yamada Y, Kohashi K, Ishihara S, Ito Y, Susuki Y, Kawaguchi K, Kinoshita I, Kiyozawa D, Mori T, Kuboyama Y, Tateishi Y, Yamamoto H, Fujiwara T, Setsu N, Endo M, Matsumoto Y, Nakashima Y, Mawatari M, Oda Y

    Pathology - Research and Practice   228 ( 153668 )   2021年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Synovial sarcoma (SS) is a malignant soft tissue neoplasm harboring SS18-SSX fusion gene and is histologically characterized by spindle cells and epithelial components. Some investigations have demonstrated that desmoplastic reaction (DR) is an independent prognostic factor of cancers. However, it remains unknown whether DR is of predictive value for the prognosis of synovial sarcoma patients. Here, we reviewed the clinical and histological findings of 88 patients with SS. We defined DR as hyalinized collagenous structures and classified the degree of DR as follows: none, mild, moderate, and severe. Overall, 23 SS cases (24%) showed moderate or severe DR histologically. Statistically, the cases with moderate or severe degree of DR showed poorer prognosis than those with no or mild DR (local recurrence: P = 0.0059, distant metastasis: P = 0.0002, tumor death: P = 0.0382). The findings of the study suggest that the DR of synovial sarcoma could be an important prognostic factor.

    DOI: 10.1016/j.prp.2021.153668.

  • Pathological review of cardiac amyloidosis using autopsy cases in a single Japanese institution. 査読 国際誌

    Tateishi Y, Yamada Y, Katsuki M, Nagata T, Yamamoto H, Kohashi K, Koga Y, Hashisako M, Kiyozawa D, Mori T, Kuboyama Y, Kakinokizono A, Miyazaki Y, Yamaguchi A, Tsutsui H, Ninomiya T, Naiki H, Oda Y

    Pathology - Research and Practice   227 ( 153635 )   2021年11月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pathological review of cardiac amyloidosis using autopsy cases in a single Japanese institution.

    DOI: 10.1016/j.prp.2021.153635.

  • The association between the expression of PD-L1 and CMTM6 in undifferentiated pleomorphic sarcoma. 査読 国際誌

    Ishihara S, Iwasaki T, Kohashi K, Yamada Y, Toda Y, Ito Y, Susuki Y, Kawaguchi K, Takamatsu D, Kawatoko S, Kiyozawa D, Mori T, Kinoshita I, Yamamoto H, Fujiwara T, Setsu N, Endo M, Matsumoto Y, Nakashima Y, Oda Y

    Journal of Cancer Research and Clinical Oncology   147 ( 7 )   2003 - 2011   2021年7月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Undifferentiated pleomorphic sarcoma (UPS) is a sarcoma with a poor prognosis. A clinical trial, SARC028, revealed that treatment with anti-PD-1 drugs was effective against UPS. Studies have reported that UPS expresses PD-L1, sometimes strongly (≥ 50%). However, the mechanism of PD-L1 expression in UPS has remained unclear. CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) was identified as a novel regulator of PD-L1 expression. The positive relationship between PD-L1 and CMTM6 has been reported in several studies. The aim of this study was thus to examine CMTM6 expression in UPS and evaluate the relationship between PD-L1 and CMTM6 in this disease.
    Materials and methods: Fifty-one primary UPS samples were subjected to CMTM6 and PD-L1 immunostaining. CMTM6 expression was assessed using proportion and intensity scores. CMTM6 gene copy number was also evaluated using a real-time PCR-based copy number assay. We also analyzed the mRNA expression and copy number variation of PD-L1 and CMTM6 in The Cancer Genome Atlas (TCGA) data.
    Results: TCGA data indicated that the mRNAs encoded by genes located around 3p22 were coexpressed with CMTM6 mRNA in UPS. Both proportion and intensity scores of CMTM6 positively correlated with strong PD-L1 expression (≥ 50%) (both p = 0.023). CMTM6 copy number gain increased CMTM6 expression. Patients with UPS with a high CMTM6 intensity score had a worse prognosis for overall survival.
    Conclusions: UPS showed variation in CMTM6 copy number and CMTM6 expression. CMTM6 expression was significantly correlated with PD-L1 expression, especially with strong PD-L1 expression.

    DOI: 10.1007/s00432-021-03616-4.

  • A validation study of whole slide imaging for primary diagnosis of lymphoma. 査読 国際誌

    Amin S, Mori T, Itoh T

    Pathology International   69 ( 6 )   341 - 349   2019年6月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Whole slide imaging (WSI) is being increasingly used worldwide. Although previous studies have asserted the validity of WSI diagnosis, they have primarily targeted only small specimens and excluded cases requiring immunohistochemistry or special staining, such as lymphoma. The purpose of this study was to evaluate the accuracy of WSI diagnosis of lymphoma, for which 240 biopsies and resections of lymphoma cases were selected from the study set of lymphomas. All slides including H&E, immunohistochemical and special staining were digitized using a WSI image scanner. An experienced pathologist performed the WSI diagnoses, which were compared with original diagnoses based on light microscopic examinations. Discrepancy between the two interpretations were classified into three categories: concordance, minor discrepancy (no clinical significance), and major discrepancy (with clinical significance). Overall concordance between the light microscopic and WSI diagnosis was found in 223 cases (92.92%; 95%CI = 88.90-95.82), minor discrepancy in fifteen (6.25%; 95%CI = 3.54-10.10), and major discrepancy in two (0.83%; 95%CI = 0.10-2.98). Diagnosis of lymphoma using WSI appeared to be mostly accurate, suggesting that WSI may be a reliable technology for the diagnosis of lymphoma.

    DOI: 10.1111/pin.12808.

▼全件表示

講演・口頭発表等

  • Tumor of the left mandible 国際会議

    Taro Mori, Ikumi Imajo, Tomohiro Yamada, Tamotsu Kiyoshima, Yoshinao Oda

    MSK 2023 Global Musculoskeletal Societies Joint Meeting  2023年10月 

     詳細を見る

    開催年月日: 2023年10月

    記述言語:英語  

    開催地:London   国名:日本国  

所属学協会

  • 日本病理学会

  • 日本臨床細胞学会

  • 日本癌学会

  • 日本臨床検査医学会

委員歴

  • 日本病理学会   評議員   国内

    2023年4月 - 2025年3月   

担当授業科目

  • 系統医学Ⅱ:病理学(総論)

    2023年4月 - 2023年9月   前期

  • 病因と病態II

    2023年4月 - 2023年9月   前期