Can microsatellite instability in early-stage gastric cancer be identified by immunohistochemical staining alone?

Research Project

Project/Area Number	18K15089
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 49020:Human pathology-related
Research Institution	Iwate Medical University
Principal Investigator	Sugimoto Ryo 岩手医科大学, 医学部, 助教 (30724869)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000) Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	胃癌 / マイクロサテライト不安定性 / 免疫組織化学染色 / MLH1 / PMS2 / MSH2 / MSH6 / 早期胃癌 / MSI
Outline of Final Research Achievements	Few reports have examined the correlation between PCR results and DNA MMR-related protein expression. Decreased expression of MLH1 is a valuable marker to predict MSI status. In some cases, MLH1 expression did not reflect MSI status. Decreased expression of PMS2 was associated with MLH1, but the degree of PMS2 downregulation was more limited than that of MLH1. Although reduced expression of PMS2 and MSH6 helps detect MMR deficiency, it is desirable to evaluate MLH1 and MSH2/MSH6 to predict MSI.IHC of MMR gene products is not a replacement for genetic testing to determine MSI status in EGCs.Based on the above results, the paper was accepted for publication in DIGESTION in 2020.
Academic Significance and Societal Importance of the Research Achievements	近年マイクロサテライト不安定性（MSI）型癌に対して免疫チェックポイント阻害薬が保険収載され注目を集めている。MSIの検出にはPCR法、免疫染色（IHC）があるが両者の関係についての検討は十分なされていなかった。今回の結果から、MLH1発現低下は、MSI状態を予測する有用なマーカーであった。また、PMS2とMSH6の発現低下はMMR欠損の検出に役立つが、MSIを予測するためにはMLH1とMSH2/MSH6を評価することが望ましい。ミスマッチ修復（MMR）遺伝子産物のIHCは早期胃癌ののMSIを判定するための遺伝子検査に代わるものではない。以上は、2020年にDIGESTIONに掲載された。