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

目的：通过研究胃癌中错配修复基因hMLH1启动子区5CpG岛甲基化及蛋白表达情况，探讨hMLH1启动子Ⅸ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）榆测标本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hMLH1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。hMLHI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。

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

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 hMLH1 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 41.46% (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.