乳腺癌患者血清中p16基因甲基化状态的研究

p16 gene promoter hypermethylation in serum DNA from breast cancer

目的选取p16基因启动子甲基化这一指标来探讨乳腺癌患者外周血清中游离的肿瘤相关DNA与肿瘤组织及临床病理参数的相关性。方法应用甲基化特异性聚合酶链反应(MS-PCR)检测82例乳腺癌患者组织及其配对血清中游离DNAp16基因启动子区域甲基化状况。结果 82例乳腺癌组织p16基因启动子甲基化阳性率为30.5%(25/82),相应外周血清中p16基因启动子甲基化阳性率为19.5%(16/82)。25例呈现甲基化阳性的癌组织中有16例其配对血清中也监测到DNA甲基化阳性,而82例乳腺癌组织中甲基化阴性的57例患者、30例乳腺良性病变患者以及24例健康人,其外周血清均为p16基因启动子甲基化阴性。外周血清中p16基因启动子区域甲基化异常与乳腺癌组织中的甲基化状况显著相关(r=0.7435,P<0.05)。乳腺癌组织及外周血清中p16基因启动子区域甲基化状态与肿瘤分期、肿块的大小、病理类型、月经状况、淋巴结转移、激素受体、家族史无关。结论乳腺癌患者外周血清中p16基因启动子甲基化与肿瘤组织中相同基因的变异显著相关,可用血清替代癌组织检测p16基因启动子区域甲基化状态。

Objective To detect p16 gene promoter hypermethylation in breast cancer tissue and paired peripheral serum,and their correlation with clinicopathologic parameters.Methods We used MS-PCR（methylation-specific polymeras chain reaction） to detect the methylation status of p16 gene promoter in tumor tissue and paired peripheral serum from 82 breast cancer patients.Results The positive rate of p16 gene promoter methylation was 30.5%（25/82）in tumor tissue and 19.5%（16/82） in paired peripheral serum.That was,in these primary tumors with methylation,64.0%（16 of 25） also had abnormal methylated DNA in the matched serum samples.Moreover,none of the sera from patients with tumors not demonstrating methylation,breast benign disease and healthy control was positive.p16 gene hypermethylation in peripheral serum was significantly correlated to that in primary tumor（r=0.7435,P0.05）.The aberrant methylation of p16 gene promoter in tumor tissues and paired peripheral serum had no correlation to patient＇s tumor staging,tumor size,histologcal type,menstruation,lymphonode metastasis,hormone receptor and family history.Conclusion The aberrant tumor gene methylation in peripheral serum of breast cancer is significantly correlated to that in primary tumor.Serum can take the place of tumor tissue to detect the methylation status of p16 gene promoter.