hMLH1和hMSH2蛋白表达在遗传性非息肉病性大肠癌诊断中的应用

目的　评价错配修复基因hMLH1和hMSH2蛋白表达在筛选遗传性非息肉病性大肠癌(HNPCC)中的价值。方法　收集大肠癌患者 6 6例 ,分为HNPCC患者 (A组 ,n =19)、高度可疑HNPCC患者 (B组 ,n =2 0 )、符合Bethesda指导标准的可疑HNPCC患者 (C组 ,n =14 )及散发性大肠癌患者 (D组 ,n =13)四组 ,用免疫组化方法检测各组错配修复基因hMLH1和hMSH2的蛋白表达。结果　A组hMLH1和hMSH2蛋白表达减低或缺失达 72 .8% ;B组为 6 0 .0 % ;C组为 2 8.4 % ;D组为 7.7%。hMLH1和hMSH2蛋白表达减低或缺失与HNPCC显著相关 (P =0 .0 0 0 8)。此外 ,hMLH1蛋白表达减低或缺失率显著高于hMSH2 (P <0 .0 1)。结论　hMLH1和hMSH2蛋白表达减低或缺失与HNPCC的可能性显著相关 ,免疫组化检测此二种蛋白表达能快速、有效地帮助临床医生评估患者HNPCC的可能性 ,同时提示相应错配修复基因存在突变。中国HNPCC患者中hMLH1基因发生突变的机会可能高于hMSH2基因。

Detection of hMLH1/hMSH2 expression for identifying patients with hereditary nonpolyposis colorectal carcinoma

Objective To evaluate the significance of expression of hMLH1 and hMSH2 in detecting hereditary nonpolyposis colorectal carcinoma (HNPCC). Methods Colorectal carcinomas from 66 patients were examined by immunohistochemistry for the expressions of hMLH1 and hMSH2 using commercially available monoclonal antibodies. Immunohistochemical patterns of tumors from 19 HNPCC patients (Group A), 20 suspected HNPCC patients (Group B), 14 patients whose clinical features conformed to the Bethesda guideline (Group C), and 13 sporadic colorectal cancer patients (Group D) were compared. Results The absence or low expression of hMLH1 and hMSH2 was revealed in 72.8% patients of group A, 60.0% in group B, 28.4% in group C and 7.7% in group D. The absence or low protein expression of hMLH1 and hMSH2 was significantly correlated with HNPCC (P=0.0008). The absence or low expression of hMLH1 was higher detection rate than that hMSH2 (P=0.01). Conclusions HNPCC patients can be identified by immunohistochemical methods according to the expression of hMLH1 and hMSH2, which may be used in clinical practice and research. Immunohistochemical analysis of hMLH1 and hMSH2 may predict the presence of corresponding gene mutations. Gene mutation in hMLH1 might be higher than that in hMSH2 in Chinese HNPCC.