散发性乳腺癌患者血浆BRCA1基因启动子异常甲基化的检测

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

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。

Purpose：To evaluate the status and diagnostic value of bypermethylated BRCAI 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 BRCAI gene were 29% and 24.7%,respectively,incancertissue 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 methrlation frequencies were seen between promenopause and postmenopause（P〉0.05）.Conclusions：Detection of bypermethylation change of BRCAI promoter promises a definte value in histologic type.malignant metastases and early prognostic in sporadic breast cancer.