Search for treatment seeds of high grade renal cell carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16875
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Osaka Metropolitan University (2023); Kansai Medical University (2019-2022)
• Principal Investigator: Ohe Chisato 大阪公立大学, 大学院医学研究科, 准教授 (40469242)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 腎細胞癌 / 融合遺伝子 / 次世代シークエンサー / 遺伝子異常 / 組織形態

Outline of Final Research Achievements

To construct an updated clinicopathological database, we re-evaluated the histological classification and stage of approximately 600 renal cancers according to the WHO classification 4th edition and TNM classification 8th edition. We could not find any cases of renal cancers with druggable driver gene mutations for which therapeutic drugs have been developed for other organs. Instead, we investigated the association of genetic abnormalities with protein expression and hematoxylin and eosin-based morphology for renal cell carcinomas. Additionally, we searched for biomarkers that could lead to prognosis prediction and current treatment selection. In clear cell renal cell carcinoma, we showed the possibility that clear and eosinophilic cytoplasm, vascularity-based architectural classification, and tumor-associated immune cells may predict the therapeutic response of anti-angiogenic inhibitors and immune checkpoint inhibitors, which are used for patients with advanced renal cancers.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

日常の病理診断で用いるHE染色標本に基づく形態的評価が、淡明細胞型腎細胞癌の治療薬の奏功性と関連する遺伝子異常と相関することを示した。遺伝子異常と組織形態の相関を検証することで、煩雑で高額な遺伝子検査に依らない簡便で再現性の高い病理学的バイオマーカーが確立できる可能性を見出した。