Immunohistochemical Analysis of Mismatch Repair Gene Proteins in Early Gastric Cancer Based on Microsatellite Status
Immunohistochemical Analysis of Mismatch Repair Gene Proteins in Early Gastric Cancer Based on Microsatellite Status
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DOI：
10.1159/000510679
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发表时间：
2021-09-01
期刊：
影响因子：
3.2
通讯作者：
Sugai, Tamotsu
中科院分区：
文献类型：
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作者：
Sugimoto, Ryo;Endo, Masaki;Sugai, Tamotsu
背景资料：微卫星不稳定性（MSI）是胃癌发生的主要途径，在10-20%的早期胃癌（EGCs）中观察到。早期检测具有MSI高表型的EGCs将有助于阐明胃癌发生机制和改善GC患者的预后。目的：我们探讨错配修复（MMR）蛋白，包括MLH 1，PMS 2，MSH 2和MSH 6在EGC免疫组化表达的有用性。研究方法：我们研究了4 MMR蛋白的表达，采用免疫组化在119例EGC患者的MS状态的基础上，通过聚合酶链反应-微卫星分析。此外，通过焦磷酸测序定量MLH 1基因的甲基化。结果：EGCs分为46个MSI高表型和73个微卫星稳定（MSS）表型。尽管在MSI高表型中MLH 1表达缺失与PMS 2表达缺失相关，但发现MLH 1和PMS 2之间表达缺失的不一致病例（MLH 1 [-]/PMS 2 [+]，3例）。在73个MSS表型中的2个中观察到MLH 1/PMS 2表达缺失。MSH 2/MSH 6表达缺失见于46个MSI高表型中的4个，而MSH 2/MSH 6表达缺失在MSS表型中未检测到。此外，MLH 1表达的缺失与MLH 1的甲基化相关。然而，也有不一致的情况下，MLH 1表达的损失并不伴随着MLH 1的甲基化。结论：虽然MMR蛋白的免疫染色可以帮助预测在EGCs的MSI，免疫染色没有相同的价值，为确定MSI的基因检测。
Background: 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. Objective: We explored the usefulness of immunohistochemical expression of mismatch repair (MMR) proteins, including MLH1, PMS2, MSH2, and MSH6 in EGC. Methods: 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. Results: 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. Conclusion: 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.