散发性乳腺癌患者血浆BRCA1基因启动子异常甲基化的检测

目的:探讨散发性乳腺癌组织及外周血浆中BRCA1基因启动子异常甲基化状况及其在散发性乳腺癌诊断中的价值。方法:用甲基化特异PCR方法对散发性乳腺癌患者癌组织、癌旁组织及相应血浆进行BRCA1异常甲基化检测。结果:93例散发性乳腺癌组织中,BRCA1基因启动子异常甲基化率为29%(27/93),相应血浆中BRCA1的甲基化检出率为24.7%(23/93),而癌旁组织、正常对照血浆未检出甲基化,只检出未甲基化的BRCA1。血浆中甲基化改变与肿瘤组织甲基化状况显著相关(P<0.05);BRCA1异常甲基化与髓样癌和粘液腺癌的组织分型显著相关(P<0.05),也与肿瘤淋巴结转移显著相关(P<0.005);但与散发性乳腺癌患者年龄(绝经与否)及肿瘤分级无显著的相关性(P>0.05)。结论:血浆BRCA1基因异常甲基化改变的检测在散发性乳腺癌的特异诊断、组织分型和淋巴结恶性转移等方面有一定的应用价值。

Detection of BRCA1 gene promoter hypermethylation in plasma of sporadic breast cancer patients

Purpose:To evaluate the status and diagnostic value of hypermethylated BRCA1 gene promoter in cancer tissue and peripheral plasma of breast cancer patients.Methods:We analyzed the hypermethylation status of BRCA1 gene in 93 sporadic breast cancer tissues,para-cancer tissues and corresponding blood plasma by methylation-specific PCR.Results:Our findings are as follows:(1) methylation rates of BRCA1 gene were 29% and 24.7%,respectively,in cancer tissue and corresponding peripheral blood plasma,which were significantly coincident and higher in tumors compared with no hypermethylation being present in para-tumor and normal plasma controls(P<0.05);(2) compared with invasive ductal and invasive lobular cancer,methylation frequencies were significantly higher in medullary and mucinous tumors(P<(0.05));(3) hypermethylation often followed lymph node metastases and unmethylated BRCA1 gene always went with lower metastases in sporadic breast cancer(P<0.005);(4)There were no correlations for tumor grade in cancer tissues and peripheral plasma(P>0.05),and also no significant differences in methylation frequencies were seen between promenopause and postmenopause (P>0.05).Conclusions:Detection of hypermethylation change of BRCA1 promoter promises a definite value in histologic type,malignant metastases and early prognostic in sporadic breast cancer.