结直肠癌C-erbB-2基因启动子CpG岛甲基化状态及其与C-erbB-2蛋白表达的关系

目的了解结直肠癌组织C—erbB-2基因启动子区CpG岛甲基化状态、C-erbB-2蛋白表达水平及两者之间的关系。方法取经病理确诊的43例结直肠癌组织和相应癌旁组织，分别用甲基化特异性聚合酶链反应（MSP）和免疫组织化学法（IHC）检测C-erbB-2启动子区CpG岛的甲基化和C-erbB-2蛋白表达水平。结果癌组织和癌旁组织中C—erbB-2启动子区CpG岛甲基化率分别为44．2％和74．4％，差异具有统计学意义（P=0．004）。癌组织和癌旁组织中C—erbB-2蛋白过度表达率分别为67．4％和27．9％，差异具有统计学意义（P=0．000）。C—erbB-2蛋白表达水平与肿瘤分期相关。结直肠癌组织C—erbB-2启动子区CpG岛甲基化状态与C—erbB-2蛋白表达水平呈显著相关（r=0．331，P=0．03）。结论结直肠癌中C—erbB-2基因启动子区CpG岛的低甲基化可能在C—erbB-2蛋白过度表达中起一定作用，有望成为有用的肿瘤分子诊断标记和治疗靶点。

The methylation status of CpG island in the promoter region of C-erbB-2 gene and the correlation of the methylation level of C-erbB-2 gene with the C-erbB-2 oncoprotein expression in colorectal carcinoma

Objective To explore the methylation status of CpG island in the promoter region of C-erbB-2 gene and the expression of C-erbB-2 oncoprotein in colorectal carcinoma tissues and realize their correlation. Methods The methylation patterns of CpG island in the promoter region of the C-erbB-2 gene in 43 pathologically confirmed carcinoma tissues and the matched adjacent tissues were detected by the methylation specific polymerase chain reaction （MSP）. The C-erbB-2 oncoprotein was examined by immunohistochemistry（IHC）. Results The methylation rate of CpG island in the promoter region of the C-erbB-2 in tumor tissues was significantly lower than that in matched adjacent tissues （44.2% vs 74.4%, P = 0. 004）. The percentage of C-erbB-2 oncoprotein overexpression was significantly higher in carcinoma tissues than that in matched adjacent tissues （67.4% vs 27.9% ,P = 0. 000）. The C-erbB-2 oncoprotein overexpression was significantly associated with clinical stage. The hypomethylation of CpG island in the promoter region of the C-erbB-2 in carcinoma tissues was correlated with C-erbB-2 oncoprotein overexpression （ r = 0. 331, P = 0.03 ）. Conclusions The hypomethylation of CpG island in the promoter region of C-erbB-2 gene would play a certain role in C-erbB- 2 oncoprotein overexpression in colorectal carcinoma and it would be a valuable marker as cancer molecular diagnosis and a therapy target.