Kyushu University Academic Staff Educational and Research Activities Database
List of Presentations
Kenichi Kohashi Last modified date:2021.08.06

Associate Professor / Department of Basic Medicine / Faculty of Medical Sciences


Presentations
1. Kenichi Kohashi, Expressions of Core Subunits of SWI/SNF Chromatin Remodeling Complex in SMARCB1/INI1-deficient Tumors, United States and Canadian Academy of Pathology, 104th Annual Meeting , 2015.03.
2. 孝橋 賢一, 遠藤 誠, 薛 宇孝, 高橋 祐介, 山田 裕一, 山元 英崇, 小田 義直, Akt-mTOR Pathway Activation Analysis in Re-Classified Pediatric SMARCB1/INI1-Deficient Tumor, United States and Canadian Academy of Pathology, 102nd Annual Meeting, 2013.03, Background: Pediatric INI1-deficient tumor including unclassified sarcoma shows a highly aggressive biological behavior and poor prognosis. The reason for such dismal prognosis is due to a poor response for well-known antitumor drugs and difficulty in diagnosis. Therefore, an investigation of novel antitumor drugs and re-classification of pediatric INI1-deficient tumor are required. Akt-mTOR pathway is known to be activated in various types of cancer, and some kinds of mTOR inhibitors are available in clinical practice. To date, however, there has been no investigation focused on Akt-mTOR pathway in pediatric INI1-deficient tumors series.
Design: We re-classified 38 pediatric INI1-deficient tumors including 26 malignant rhabdoid tumors (MRT), 4 atypical teratoid/rhabdoid tumors (AT/RT) and 8 extra-CNS unclassified sarcomas (US), according to various immunohistochemical and microRNA statuses, and analyzed the activation status of the Akt/mTOR pathway such as phosphorylated-Akt (p-Akt), p-mTOR, p-S6RP and p-4E-BP1.
Results: Histologically, these cases were re-classified into the three groups, such as “conventional type” morphologically identical to MRT, “atypical teratoid/rhabdoid (AT/R) type” morphologically identical to CNS AT/RT, and “small cell type” characterized by a proliferation of small rounded cells having scant cytoplasm without rhabdoid cells. Conventional type, AT/R type and small cell type were 26 cases (26/26 MRTs), 6 cases (4/4 AT/RTs and 2/8 USs) and 6 cases (6/8 USs), respectively.
Immunohistochemical expressions for vimentin and epithelial markers were common features in conventional, AT/R and small cell type cases. In addition, microRNA analysis demonstrated that 5 conventional type cases and 1 small cell type case had
very close profiles (Peason’s correlation coefficient: 0.7955). Immunohistochemical positive expressions of p-Akt, p-mTOR, p-S6RP and p-4E-BP1 were observed in 20% (conventional, 15%; AT/R, 20%; small cell, 40%), 30% (conventional, 15%; AT/R, 80%; small cell, 40%), 77% (conventional, 75%; AT/R, 100%; small cell, 60%) and 37% (conventional, 25%; AT/R, 80%; small cell, 40%) of pediatric INI1-deficient tumors.
Conclusions: All extra-CNS US cases can be included to the concept of MRT, because of common immunohistochemical phenotypic expression and microRNA statuses between US and MRT. Akt-mTOR pathway was highly activated in AT/R type, compared with conventional type. Therefore, mTOR inhibitor can be a novel candidate for therapeutic target in AT/R type, and this new classification can contribute to the treatment strategy of pediatric INI1-deficient tumor..