散发性三阴乳腺癌中BRCA1启动子甲基化与蛋白表达

METHYLATION STATUS OF BRCA1 PROMOTER AND EXPRESSION OF BRCA1 PROTEIN IN SPORADIC TRIPLE NEGATIVE BREAST CANCER

目的:通过检测散发性三阴乳腺癌(TNBC)中乳腺癌易感基因(breast cancer susceptibility gene 1,BRCA1)启动子甲基化和蛋白表达,探讨BRCA1与散发性TNBC的关系。方法:应用重亚硫酸盐测序PCR(bisulfite sequencing PCR,BSP)法检测50例散发性TNBC组织及配对癌旁组织中BRCA1启动子甲基化状态,用免疫组织化学方法检测上述组织中BRCA1蛋白的表达情况,分析BRCA1启动子甲基化与蛋白表达的相关性。结果:散发性TNBC组织中BRCA1启动子甲基化率为42.0%(21/50),癌旁组织未检测出甲基化,两者比较差异有统计学意义(P=0.000)。BRCA1蛋白在散发性TNBC癌组织中的表达率为32.0%(16/50),明显低于癌旁组织68.0%(34/50)(P<0.05)。散发性TNBC癌组织中BRCA1蛋白表达与启动子甲基化呈负相关(r=-0.323,P=0.022)。结论:BRCA1启动子的高甲基化引起BRCA1蛋白表达下降或缺失,可能是散发性TNBC重要的发病机制之一。

Objective：To explore the relationship between BRCA1 and sporadic triple negative breast cancer by detecting expression and promoter methylation status of BRCA1 in sporadic triple negative breast cancer.Methods：The methylation status of BRCA1 promoter were detected in 50 cases of sporadic triple negative breast cancer and the adjacent breast tissues using bisulfite genomic sequencing PCR （BSP） combined with TA clone for sequencing.The expression of BRCA1 protein in those tissues was detected by immuno histochemical staining respectively.The relation between BRCA1 expression in sporadic triple negative breast cancer and promoter methylation status was analyzed.Results：The methylation rate of BRCA1 pro moter CpG was 42.0％ （21/50） in sporadic triple negative breast,while it wasn＇t found in adjacent breast tissues （P =0.000）.The expression positive rates of BRCA1 protein were 32.0％ （16/50） in sporadic tri ple negative breast tissue,which were significantly lower than those of in the adjacent breast tissues 68.0％ （34/50,P ＜0.001）.The statistical analysis showed that the expression of BRCA1 had significant negative correlation with promoter methylation （r =-0.323,P =0.022）.Conclusion：The hypermethylation of BRCA1 promoter could induce BRCA1 down-regulating,which may be one of important pathogenic mechanism of sporadic triple negative breast cancer.