Analyses of carcinogenesis in dedifferentiated endometrial carcinoma by using organoid and whole genome sequencing.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09472
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya City University (2023); Shimane University (2021-2022)
• Principal Investigator: Nakayama Kentaro 名古屋市立大学, 医薬学総合研究院(医学), 教授 (70346401)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 子宮体癌 / 脱分化癌 / オルガノイド

Outline of Final Research Achievements

DDEC (dedifferentiated endometrial carcinoma: DDEC) is a tumor that is a mixture of grade 1 and 2 highly differentiated endometrial carcinoma and undifferentiated carcinoma and has a worse prognosis than grade 3 endometrial adenocarcinoma. DDEC is a newly introduced concept in the 2014 WHO classification, and is thought to be a process of dedifferentiation of highly differentiated adenocarcinoma into undifferentiated carcinoma, but the molecular mechanism is still unknown. In this study, we found that DDEC is more common than other histologic types in Japan and has an extremely poor prognosis compared to other histologic types. In addition, the Tumor Mutation Burden (TMB) was extremely increased in histologically dedifferentiated areas of DDEC, indicating that immune checkpoint inhibitors may be effective.

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Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

子宮脱分化型類内膜癌は2006年にSilvaらにより提唱された新しい概念、分類である。Grade 1, 2の高分化型類内膜癌と未分化癌が混在する腫瘍と定義され、2014年のWHO改定で新たに分類された。臨床病理学的、予後に関して詳細な検討は世界でもなされておらず、未だ不明な点が多い。しかし、本研究によよって他の組織型に比べて極めて予後不良であることが明らかとなった。さらに、組織学的に脱分化の部分では遺伝子変異量：Tumor mutation burden(TMB)が極めて増加しており、免疫チェックポイント阻害剤が有効である可能性が示された。