散发性大肠癌的错配修复缺陷研究

目的探讨错配修复缺陷的散发性大肠癌的临床病理特征及错配修复缺陷检测手段的应用。方法对71例散发性大肠癌行hMLH1启动子甲基化检测、微卫星不稳定检测以及hMLH1和hMSH2的免疫组化检测,分析错配修复缺陷的散发性大肠癌的临床病理特征,探讨三种检测方法的应用价值。结果hMLH1基因启动子甲基化、微卫星不稳定和错配修复蛋白表达的阳性率分别为9.9%,9.9%和71.0%,三者密切相关。hMLH1启动子甲基化和微卫星不稳定的散发性大肠癌均具有结肠癌多发和低分化腺癌相对多见的特征。错配修复蛋白表达阴性的散发性大肠癌仅具有低分化腺癌相对多见的特征。结论错配修复缺陷的散发性大肠癌具有结肠癌和低分化腺癌多发的倾向,hMLH1启动子甲基化和微卫星不稳定以及错配修复蛋白的失表达三者密切相关。

The study of the mismatch repair deficiency of sporadic colorectal cancer

Objective To explore the clinicopathologic features of sporadic colorectal cancers with mismatch repair deficiency and the application of the methods detecting the status of mismatch repair deficiency. Methods Detecting the methylation of the hMLH1 promotor, microsatellite instability and the expression of the hMLH1 and hMSH2 proteins among 71 sporadic colorectal cancer patients, evaluating these three approaches and summarizing the clinicopathologic characteristics of sporadic mismatch repair deficient colorectal cancers. Results The positive rate of the hypermethylation of the hMLH1 promotor, microsatellite instability and the expression of the hMLH1 and hMSH2 proteins were 9.9, 9.9 and 71 percent respectively. Sporadic colorectal cancers with the hypermethylation of the hMLH1 promotor or microsatellite instability were more likely to happen to the colon and to be poorly- differentiated adenocarcinomas. Sporadic colorectal cancers with the loss of hMLH1 or hMSH2 proteins were prone to be poorly- differentiated adenocarcinomas. There was a close relationship among the hypermethylation of the hMLH1 promotor, microsatellite instability and the silencing expression of the hMLH1 proteins. Conclusions Sporadic colorectal cancers with mismatch repair deficiency are inclined to occur to the colon and to have poor differentiation. The hypermethylation of the hMLH1 promotor, microsatellite instability and the loss of the hMLH1 or hMSH2 proteins are correlated intimately to each other.