胃癌组织hMLH1启动子甲基化是造成其蛋白表达降低的主要原因

Effect of the promoter methylation on the protein expression of hMLH1 in gastric cancer

目的:通过研究胃癌中错配修复基因hMLH1启动子区5'CpG岛甲基化及蛋白表达情况,探讨hM-LH1启动子区甲基化对蛋白表达的影响及在胃癌发病中的作用。方法:收集诊断明确且未经放化疗的胃癌手术切除标本41例及同病例癌旁黏膜。应用免疫组化SP法检测标本hMLH1蛋白表达情况。应用甲基化特异性PCR(MSP)检测标本hMLH1启动子区甲基化情况。结果:胃癌组与癌旁组,hMLH1蛋白阳性表达率分别为58.54%(24/41)和80.49%(33/41)(P<0.05);启动子甲基化率分别为80.49%(33/41)和24.39%(10/41)(P<0.05);完全甲基化率分别为41.46%(17/41)和19.51%(8/41)(P<0.05);部分甲基化率分别为39.02%(16/41)和4.88%(2/41)(P<0.05)。无论胃癌组织还是癌旁组织,完全甲基化病例均出现hM-LH1蛋白表达缺失,部分甲基化病例和启动子未甲基化病例均有hMLH1蛋白表达。hMLH1基因启动子甲基化率与胃癌患者性别、年龄、癌组织分化程度、浸润深度和淋巴结转移均无明显相关性(P>0.05)。结论:hM-LH1基因启动子甲基化是导致hMLH1蛋白表达降低的主要原因;胃黏膜hMLH1蛋白表达降低有助于胃癌的预警。

Objective：To study the effect of the promoter methylation on the protein expression of hMLH1 in gastric carcinoma and to explore its action in gastric carcinogenesis. Methods： Immunohistochemistry was used to examine the hMEH1 protein expression in 41 cases of gastric carcinoma and corresponding adjacent mucosa. Methylation - specific PCR （MSP） was used to examine the hMLH1 promoter methylation state in all cases. Results： The positive expression rates of hMLH1 protein in gastric carcinoma and adjacent mucosa were 58.54% （24/41） and 80.49% （33/41） respectively （ P 〈 0. 05 ）, the positive rates of promoter methylation were 80.49% （33/41） and 24.39% （10/41） respectively（P 〈0.05 ）. The rates of total -methylation in gastric carcinoma group and adjacent mucosa group were 4l. 46% （ 17/41 ） and 19.51% （8/41） respectively （P 〈 0.05 ）, the positive rates of partial - methylation were 39.02% （ 16/41 ） and 4.88% （2/41） respectively （ P 〈 0.05）. The rate of hMLH1 promoter methylation was not significantly related to sex, age of patients, tissue differentiation, invading deepth and lymphonode metastasis of carcinoma （P 〉 0.05）. Conclusion： hMLH1 gene promoter methylation is a major cause of protein expression reduction.