Biological stratifications in SWI/SNF chromatin-remodeling complex-related tumors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06887
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Osaka Metropolitan University (2023); Kyushu University (2021-2022)
• Principal Investigator: KOHASHI Kenichi 大阪公立大学, 大学院医学研究科, 教授 (10529879)
• Co-Investigator(Kenkyū-buntansha): 山田 裕一 九州大学, 医学研究院, 講師 (00597643) ; 木下 伊寿美 九州大学, 大学病院, 医員 (50766186) ; 小田 義直 九州大学, 医学研究院, 教授 (70291515)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: SMARCB1 / SWI/SNF / epithelioid sarcoma / myxoepithelioid tumor

Outline of Final Research Achievements

Tumors with complete loss of SMARCB1 expression, such as epithelioid sarcoma, have an extremely poor prognosis. However, we have identified specific tumor group with complete loss of SMARCB1 (myxoepithelioid tumor, MET) that have a relatively good prognosis, and predominantly occur in the vulvar region of women. Histologically, METs are distinguishable from epitheliosarcomas in that they are relatively well demarcated and positive for ER and PgR. Genetically, these two tumors have significantly different mRNA profiles in cluster analysis, with METs having significantly elevated AR as well as ER and PgR. On the other hand, epithelioid sarcomas show high expression of tumor immune-related genes such as IDO-1, suggesting the usefulness of immune checkpoint inhibitors.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

類上皮肉腫は予後不良の高悪性度軟部腫瘍であり、治療では広範切除に加えて化学療法や放射線治療など高度の侵襲的治療が選択されていた。しかし、その中で比較的予後良好な腫瘍群（myxoepithelioid tumor, MET）が見いだされ、類上皮肉腫とは分子生物学的背景も異なることが証明された。これらの腫瘍の治療には、侵襲的治療は限定的でよい可能性があり、社会的意義は大きいと考える。また、組織学的鑑別法という点でも、ERやPgRが有用であることを見出しており、鑑別は容易に行いうる点も意義があると考える。