【摘要】 目的检测4种不同分子亚型乳腺癌(腺腔A型、腺腔B型、基底样型和HER-2过表达型)中的p16蛋白表达和启动子甲基化状态及其与临床病理参数的关系,探讨p16甲基化在乳腺癌发生、发展中的意义。方法分别采用免疫组化PV法和甲基化特异性PCR(MSP)法检测73例乳腺癌组织中p16蛋白表达和启动子甲基化水平,并分析其与临床病理参数的关系。结果 (1)腺腔A型、腺腔B型、HER-2过表达型及基底样型乳腺癌中p16蛋白阳性率分别为55%、35%、30%和15.4%,甲基化率分别为10%、25%、10%和46.2%。基底样型乳腺癌中的p16蛋白阳性率最低,与腺腔A型差异有显著性(P<0.05),而甲基化率最高,与腺腔A型和HER-2过表达型差异均有显著(P<0.05)。(2)p16启动子甲基化、无甲基化的乳腺癌组中p16蛋白阳性率分别为13.3%和41.4%,差异有统计学意义(P<0.05)。(3)淋巴结转移组p16基因的甲基化率为29.3%,明显高于无淋巴结转移组(9.4%)(P<0.05)。(4)p16甲基化率随着组织学分级增高而增高,组织学Ⅰ级乳腺癌p16甲基化率明显低于组织学Ⅱ、Ⅲ级乳腺癌(P<0.05)。结论 p16基因启动子甲基化可能是基底样型乳腺癌分子特征之一,并与乳腺癌进展相关。更多还原

【Abstract】 Purpose To detect the p16 gene protein expression and promoter methylation in 4 subtypes of breast cancer: luminal A,luminal B,basal-like and HER-2 overexpressing phenotype,and evaluate the relationship between p16 methylation and clinicopathological parameters,which aim to explore the significance of p16 methylation in breast cancer.Methods p16 gene expression and promoter methylation were examined in 73 breast cancers using immunohistochemistry and methylation specific PCR(MSP) methods.The results were correlated with clinicopathological parameters.Results The frequency of p16 protein expression in luminal A,luminal B,HER-2 overexpression and basal-like phenotype was 55%,35%,30% and 15.4%,respectively,and the methylation rate was 10%,25%,10% and 46.2%,respectively.Basal-like tumors showed the lowest p16 expression and the highest p16 methylation rate.The difference of p16 expression is significant between basal-like and luminal A tumors(P<0.05),the difference of p16 methylation is significant between basal-like tumors and both luminal A and HER-2 overexpression tumors(both P<0.05).13.3% tumors with p16 promoter methylation expressed p16 protein,which was significantly lower than that of tumors without p16 methylation(41.4%)(P<0.05).29.3 % breast cancers with lymph node metastasis showed p16 methylation,which was significantly higher than breast cancers wihout lymph node metastasis.p16 methylation rate in grade Ⅰ breast cancers was significantly lower than that of grade Ⅱ and Ⅲ breast cancers(P<0.05).Conclusion p16 gene promoter methylation is one of the specific features of basal-like breast tumors,and maybe associated with the progression of breast carcinomas.更多还原