乳腺癌组织与血清BRCA1基因异常甲基化的临床意义

目的:探讨乳腺癌BRCA1基因启动子异常甲基化状况及其在乳腺癌早期诊断中的价值。方法:用甲基化特异PCR方法对乳腺癌患者癌组织、癌旁组织及对应血浆进行BRCA1异常甲基化检测。结果:乳腺癌组织中BRCA1启动子异常甲基化检出频率为35/102(34%),血浆的检出率为32/102(32%),而癌旁组织中没有检出BRCA1异常甲基化。根据不同病理特征将35例散发性乳腺癌按组织类型、不同分级、有无淋巴结转移和年龄进行分类分析。结果显示,MSP法检测肿瘤组织与对应血浆BRCA1异常甲基化有很好的一致性(P>0.05)。102例患者的组织与血清中甲基化检出率的一致性良好(Kappa=0.765)。BRCA1基因甲基化结合病理特征表明,BRCA1基因在原位癌中甲基化检出率明显低于浸润性癌(P<0.05),有淋巴结转移相应标本BRCA1基因甲基化检出率也明显高于无淋巴结转移的标本(P<0.05),而BRCA1基因甲基化与否与肿瘤分级及年龄(绝经前后)无明显关联(P>0.05)。结论:BRCA1基因异常甲基化在乳腺癌组织与血清有相似的甲基化模式,且在乳腺癌的组织分型与转移方面有一定的鉴别诊断价值。

Aberrant Hypermethylation Profile of BRCA1 in Tissue and Serum of Breast Carcinogensis

Objective:To investigate the status of hypermethylated BRCA1 promoter in sporadic breast cancer and the value in clinical early diagnosis.Methods:The hypermethylation status of BRCA1 gene was detected in 102 sporadic breast cancer tissues,para-tumor tissue and blood plasma of normal subjects and breast cancer patients by methylation-specific PCR.Results:①Methylation rates of BRCA1 gene were 35% and 32% in cancer tissue and corresponding peripheral blood plasma respectively,while there were no hypermethylation was found in para-tumor tissues and in normal plasma controls.②Compared with primary cancer,methylation frequencies were significantly higher in invasive carcinoma(P<0.005).③Hypermethylation of BRCA1 was related with lymph node metastases.④ No significant differences in methylation frequencies were seen between pre-menopause and post-menopause or among different tumor grades (P>0.05).Conclusion:Aberrant hypermethylation of BRCA1promoter region is valuable for the determination of histological type and malignant metastases of breast cancer.