Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Shiwa, Japan.
Department of Internal Medicine, Division of Gastroenterology, School of Medicine, Iwate Medical University, Shiwa, Japan.
Digestion. 2021;102(5):691-700. doi: 10.1159/000510679. Epub 2020 Oct 14.
Microsatellite instability (MSI) is a major pathway involved in gastric carcinogenesis and is observed in 10-20% of early gastric cancers (EGCs). Early detection of EGCs with an MSI-high phenotype would be useful for elucidating the mechanisms of gastric carcinogenesis and improving outcomes in patients with GC.
We explored the usefulness of immunohistochemical expression of mismatch repair (MMR) proteins, including MLH1, PMS2, MSH2, and MSH6 in EGC.
We examined the expression of 4 MMR proteins using immunohistochemistry in 119 patients with EGC based on MS status, as determined by polymerase chain reaction-microsatellite analysis. In addition, methylation of the MLH1 gene was quantified by pyrosequencing.
EGCs were classified into 46 MSI-high phenotypes and 73 microsatellite stable (MSS) phenotypes. Although loss of MLH1 expression was associated with loss of PMS2 expression in the MSI-high phenotype, discordant cases of loss of expression between MLH1 and PMS2 were found (MLH1 [-]/PMS2 [+], 3 cases). Loss of MLH1/PMS2 expression was observed in 2 of 73 MSS phenotypes. Loss of MSH2/MSH6 expression was found in 4 of 46 MSI-high phenotypes, whereas loss of MSH2/MSH6 expression was not detected in the MSS phenotype. In addition, loss of MLH1 expression was correlated with methylation of MLH1. However, there were discordant cases in which loss of MLH1 expression was not accompanied by methylation of MLH1.
Although immunostaining of MMR proteins could help predict MSI in EGCs, immunostaining did not have the same value as genetic testing for determination of MSI.
微卫星不稳定（MSI）是胃癌发生的主要途径之一，在 10-20%的早期胃癌（EGC）中观察到。高 MSI 表型的 EGC 早期检测有助于阐明胃癌发生的机制，并改善 GC 患者的预后。
我们探讨了免疫组化表达错配修复（MMR）蛋白，包括 MLH1、PMS2、MSH2 和 MSH6 在 EGC 中的作用。
我们根据聚合酶链反应-微卫星分析确定的 MS 状态，用免疫组化法检测了 119 例 EGC 患者中 4 种 MMR 蛋白的表达。此外，通过焦磷酸测序定量 MLH1 基因的甲基化。
EGC 分为 46 例 MSI 高表型和 73 例微卫星稳定（MSS）表型。虽然在 MSI 高表型中 MLH1 表达缺失与 PMS2 表达缺失相关，但在 MLH1 和 PMS2 之间发现了表达不一致的病例（MLH1 [-]/PMS2 [+]，3 例）。在 73 例 MSS 表型中发现 2 例 MLH1/PMS2 表达缺失。在 46 例 MSI 高表型中发现 4 例 MSH2/MSH6 表达缺失，而在 MSS 表型中未检测到 MSH2/MSH6 表达缺失。此外，MLH1 表达缺失与 MLH1 甲基化相关。然而，有一些不一致的病例，MLH1 表达缺失并不伴有 MLH1 甲基化。
虽然 MMR 蛋白的免疫染色有助于预测 EGC 中的 MSI，但免疫染色在确定 MSI 方面不如基因检测有价值。
