错配修复基因hMSH2和hMLH1在胃癌组织中的表达及其与幽门螺杆菌感染的关系

Expression of hMSH2 and hMLH1 in Stomach Cancer and Their Correlation with Helicobactor pylori Infection

背景与目的:胃癌是一种多因素相关疾病,幽门螺杆菌(Helicobactorpylori,HP)感染是导致胃癌发生的原因之一,但其分子机制不明。错配修复基因是保证DNA复制高保真度的重要基因,与消化道肿瘤发生具有密切关系。本研究通过检测HP感染和非感染胃癌组织及癌旁粘膜组织和慢性浅表性胃炎粘膜组织中错配修复基因hMSH2和hMLH1蛋白的表达,探讨hMSH2、hMLH1基因在胃癌发生中的作用和HP致癌的可能机制。方法:采用尿素酶快速检验法对HP感染情况进行检测;利用免疫组化方法检测胃癌及癌旁粘膜和胃炎粘膜组织中hMSH2和hMLH1的表达情况,采用χ2检验对数据进行统计学分析。结果:hMSH2在胃癌组织中的阳性率(67.1%),显著高于癌旁粘膜组织(35.5%)和胃炎粘膜组织(42.1%)(P<0.05),而后两者无显著性差异(P>0.05)。癌组织中低分化腺癌的hMSH2阳性率(81.1%)显著高于高中分化腺癌(54.5%)和粘液癌(52.9%)(P<0.05);后两者间无显著性差异(P>0.05)。hMLH1的阳性率在胃癌组织(81.6%)、癌旁粘膜组织(90.8%)和胃炎组织(89.5%)间无显著性差异(P>0.05)。hMLH1在粘液癌中的阳性率(47.1%)显著低于高中分化腺癌(81.8%)和低分化腺癌(97.3%)(P<0.05),而后两者间无显著性差异(P>0.05)。在HP感染和非感染胃癌组织中,hMSH2的阳性率分别为56.8%和81.3%,

BACKGROUND &OBJECTIVE: The carcinogenesis of gastric carcinoma is related to many factors. Helicobacter pylori (HP) infection is one of the factors causing gastric carcinoma, but the exact molecular mechanism is not clear. Mismatch repair genes are important in keeping the accuracy of DNA replication. They are associated with carcinogenesis of alimentary canal. In order to investigate the role of hMSH2 and hMLH1 in stomach cancer and the possible mechanism of carcinogenesis caused by HP infection, we tested cancer tissue, surrounding mucosa and chronic superficial gastritic mucosa with and without HP infection. METHODS: HP infection was determined with quick ureolytase method. Immunohistochemistry staining was used to exam the expression of hMSH2 and hMLH1 in tumor tissue and their surrounding mucosa and gastric mucosa. Chi square was used for statistic analysis. RESULTS: The positive rate (67.1%) of hMSH2 expression in cancer tissue was significantly higher than those of surrounding mucosa (35.5%) and gastritic mucosa (42.1%) (P< 0.05); the positive rate (81.1%) of hMSH2 expression in poor differentiation group was significantly higher than those in well middle differentiation group (54.5%) and mucoid carcinoma group (54.5%) (P< 0.05), but there was no significant difference between the latter two groups. There was no significant difference among the positive rates of hMLH1 expression in cancer tissue (81.6%), in surrounding mucosa (90.8%), and in gastritic mucosa (89.5%) (P>0.05). The positive rate (47.1%) of hMLH1 expression in mucoid carcinoma group was significantly higher than those in well middle differentiation group (81.8%) and poor differentiation group (97.3%) (P< 0.05), but there was no significant difference between the latter two groups (P>0.05). In cancer tissue, the positive rate (56.8%) of hMSH2 expression in HP infection group was significantly lower than that without HP infection group (81.3%) (P< 0.05); the positive rates of hMLH1 expression was 77.2%in HP infection group and 87.5%in without HP infection group, but there was no significant difference between two groups (P >0.05). In surrounding mucosa, the positive rate of hMSH2 expression was 29.5%in HP infection group and 43.8%in without HP infection group, as well as those of hMLH1 were 86.4%and 96.9%, there were no significant differences between the groups. In gastritic mucosa, the positive rate of hMSH2 expression was 38.5%in HP infection group and 50.5%in HP negative group, as well as those of hMLH1 were 88.5%and 91.7%; there was no significant difference between the groups. CONCLUSION: The expression of hMSH2 is associated with carcinogenesis of stomach cancer, and its high expression may be a potential marker of stomach cancer; HP infection inducing low expression of hMSH2 and hMLH1 may be one of molecular mechanisms by which HP infection leads to stomach cancer.