结直肠癌组织E-钙黏附素蛋白表达与甲基化的关系

Relationship and Significance of Expression of E-cadherin Proteins and Methylation of Promoter in Colorectal Cancer Tissues

【目的】探讨结直肠癌E-钙黏附素(E-cad)蛋白表达与基因甲基化的关系及临床意义。【方法】联合采用免疫组化方法(S-P法)和甲基化特异性聚合酶链反应(MSP)方法检测100例结直肠癌肿瘤组织E-cad蛋白表达和基因启动子甲基化情况。免疫组化结果根据阳性肿瘤细胞数的百分比来判断结果:阴性(-):无表达;弱阳性(+):阳性细胞<25%;阳性(++):阳性细胞数25%～75%;强阳性(+++):阳性细胞数>75%。联合(-)和(+)为低表达病例,(++)和(+++)为高表达病例作统计分析,分析蛋白表达与甲基化的相关性及意义。【结果】100例结直肠癌组织中,33例检测到E-cad基因启动子甲基化(33%);E-cad蛋白表达的阳性率为76%(+～+++),其高表达率为59%(59/100),低表达率为41%,主要表现为腺细胞膜着色和胞浆边缘着色,少量间质细胞较少阳性,肿瘤细胞着色不均匀,且丧失极性。在41例E-Cad蛋白低表达的标本中,28例基因甲基化阳性(68.3%),E-Cad蛋白表达与甲基化呈明显负相关(P<0.001)。【结论】E-Cad蛋白的低表达或失表达可能是其基因甲基化的结果;E-Cad蛋白的表达异常是结直肠癌转移性增强的重要影响因素之一。

[ Objective ] To explore the relationship between methylation of promoter and the expression of E-cadherin proteins in eoloreetal cancer. [Methods] Streptavidin-peroxidase （S-P） two-step method was used to measure the immunohistoehemieal expression of E-cadherin proteins in 100 CRC. Those slides exhibiting diffuse immunostaining presenting more than 75% of tumor cells were classified as （＋＋＋）, between 50% and 75% were classified as （＋＋）, between 25% and 50% were classified as （＋）, and those with immunoreactivity less than 10% were classified as （-）. （-） and （＋） were combine together as lower expression cases, while （＋＋） and （＋＋＋） were combined together as higher expression cases for statistical analysis. [ Results ] The positive rate of E-cadherin proteins was 76% （＋ - ＋＋＋ ） in 100 sporadic eolorectal cancer specimen. Fifty-nine cases showed higher expression of E-cadherin, while decreased E-cadherin immunohistochemical expression was observed in 41 eases. The methylation positive rate was 68.3% of E- eadherin was significant association with protein decreased expression of E-eadherin gene （P 〈 0.001 ）. [ Conclusion] Methylation of E-cadherin gene was significant association with E-cadherin protein decreased expression. The loss of E-cadherin protein was one of the important influence factors in colorectal cancer metastatic and invasive.