Molecular analysis of duodenal carcinogenesis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07401
• 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: National Cancer Center Japan
• Principal Investigator: Shigeki Sekine 国立研究開発法人国立がん研究センター, 中央病院, 医長 (10321879)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 十二指腸 / 腺腫 / 腺癌

Outline of Final Research Achievements

A total of 144 duodenal adenomas and 54 adenocarcinomas were subjected to analysis for immunohistochemical phenotypes, mismatch repair status, and genetic alterations. It was observed that APC mutations were frequent in adenomas but rare in adenocarcinomas, indicating that clinically detected adenomas were generally associated with a low risk of malignant progression. Furthermore, distinct genetic alterations were found in specific adenoma subtypes, supporting the validity of the current morphological classification. Notably, GNAS mutations were identified as a genetic characteristic of gastric-type adenomas and adenocarcinomas. Additionally, a high frequency of mismatch repair deficiency was observed in adenocarcinomas, underscoring the clinical significance of mismatch repair deficiency testing.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

現在臨床的に切除されている十二指腸腺腫の多くが、比較的浸潤癌への進展リスクの低い病変であることが示唆された。また、十二指腸発癌の発生経路の分子生物学的多様性がより明らかになった。十二指腸癌はミスマッチ修復異常を示す腫瘍の頻度が高く、その検索の臨床的意義が高いと考えられた。