食管癌组织hMSH2 mRNA的表达和启动子区甲基化

Expression and promoter methylation of hMSH2 gene in esophageal cancer tissue

目的:检测食管癌组织中hMSH2 mRNA的表达和启动子区甲基化异常.方法:食管癌标本及相应正常食管黏膜组织32例.原位杂交法检测hMSH2 mRNA的表达,甲基化特异PCR(MSP)法检测错配修复基因hMSH2启动子区甲基化.结果:食管癌组织中hMSH2 mRNA阳性表达率为46.9%,正常组织为84.4%(P<0.05).hMSH2 mRNA阳性表达率与食管癌患者年龄、性别、肿瘤大小、肿瘤位置、病理类型、组织学分级、淋巴结转移、浸润深度等均无关(P>0.05).食管癌组织中hMSH2启动子区甲基化发生率为34.4%,正常食管黏膜组织未发现甲基化,2组甲基化阳性率相比较差异有统计学意义(P<0.01);高龄患者(≥70岁)癌组织中hMSH2启动子区甲基化发生率(85.7%)明显高于较低龄患者(<70岁)(20.0%)(P<0.05);病理组织学Ⅲ,Ⅳ级食管癌组织中hM-SH2启动子区甲基化发生率(70.0%)高于Ⅰ,Ⅱ级(18.2%)(P<0.05).食管癌组织中hMSH2 mRNA阳性组启动子区甲基化的发生率(13.3%)低于hMSH2mRNA表达阴性组(53.0%)(P<0.05).结论:hMSH2的表达缺失是食管癌发生的早期事件;食管癌组织中hMSH2基因启动子区甲基化与患者年龄和肿瘤病理类型可能有关;hMSH2基因的失活与其甲基化有一定关系.

AIM： To detect hMSH2 gene expression and test abnormal methylation of hSMH2 gene promoter in esophageal cancer tissue. METHODS： In situ hybridization （ISH） and methylation-specific PCR （MSP） methods were respectively used to detect hMSH2 gene expression and hMSH2 promoter methylation in 32 cases of esophageal cancer and the corresponding normal tissues. RESULTS ： The positive rate of hMSH2 was 46.9% in esophageal cancer tissues, which was significantly lower than that in the normal tissues （84.4%, P 〈 0.05 ）. The positive rate of hMSH2 gene in esophageal cancer tissues had a weak correlation with age, sex, tumor size and location, pathological type, histological grade, lymph node metastasis （ Spread）, and tumor infiltration depth （ P 〉 0.05 ）. The occurrence rate of hMSH2 promoter methylation was 34.4% in esophageal cancer tissues, no methylation was found in normal esophageal tissues, and there was a significant difference in the incidence of promoter methylation between the 2 groups （ P 〈 0.01 ）. The positive rate of promoter methylation in elder patients （age ≥70 years, 85.7% ） was much higher than that in younger patients （ age 〈 70 years, 20.0% , P 〈 0.05 ） ; hMSH2 promoter methylation rate （ 70.0% ） in the patients with tissue pathological level of Ⅲ-Ⅳwas much higher than that in the patients with level ofⅠ-Ⅱ （18.2%, P〈0.05）. The positive rate of promoter methylation in esophageal cancer tissues with positive expression of hMSH2 gene （ 13.3% ） was significantly lower than that in esophageal cancer tissues with negative expression （ 53.0%, P 〈 0. 05 ）. CONCLUSION： hMSH2 gene inactivation appears at the early stage of esophageal cancer, hMSH2 gene promoter methylation is related to patient＇s age and tumor pathological type, and hMSH2 gene inactivation is related to the methylation of promoter.