Abstract: Objective　To analyze the promoter methylation status of GSTP1，BRCA1 and MGMT in breast cancer tissues and its correlation with clinical pathological features.Methods　According to the inclusion criteria，we enrolled 100 cases of breast cancer from the Second Affiliated Hospital of Hainan University from January 2015 to June 2016.The promoter methylation status of GSTP1，BRCA1 and MGMT in breast cancer tissues and tissues adjacent to breast cancer was detected by methylation-specific PCR and its relationship with clinical pathological features was analyzed.Cox regression analysis was performed to investigate the relationship between the promoter methylation status and prognosis of the patients.Results　Promoter methylation level of GSTP1，BRCA1 and MGMT in breast cancer tissues was higher than that in tissues adjacent to breast cancer（P<0.05）.The proportion of methylated genes in breast cancer tissue was higher than that of the methylated breast cancer adjacent tissue （P<0.05）.The promoter methylation level of these genes differed significantly by breast cancer staging and prevalence of lymphatic metastasis（P<0.05）.Patients with breast cancer of≥20 mm in maximum diameter showed higher methylation level in the promoter region of GSTP1 compared with those with breast cancer of <20 mm in maximum diameter（P<0.05）.Moreover，breast cancer patients with lymphatic metastasis presented higher methylation level in the promoter region of GSTP1 compared with those without（P<0.05）.Younger than 50 years old and estrogen receptor negative were associated with higher methylation level in the promoter region of BRCA1（P<0.05）.Patients with histological Ⅲbreast cancer，stage Ⅱ-Ⅳ breast cancer or breast cancer with lymphatic metastasis demonstrated higher methylation level in the promoter regions of MGMT compared with those with histological Ⅰ-Ⅱ breast cancer，stage Ⅰ breast cancer or breast cancer without lymphatic metastasis（P<0.05）.Cox regression analysis showed that the methylation in the promoter regions of GSTP1，BRCA1 and MGMT genes were associated with the prognosis of breast cancer （P<0.05）.Conclusion　The promoter regions of GSTP1，BRCA1 and MGMT in breast cancer tissue was higher than that of the methylated breast cancer adjacent tissue.The methylation of GSTP1，BRCA1 and MGMT genes are correlated with clinicopathological characteristics and progression of breast cancer.

Key words: Breast neoplasms, Gene methylation, Tissue detection, Pathology

摘要： 目的　分析乳腺癌组织中胱甘肽S转移酶P1（GSTP1）、乳腺癌易感基因1（BRCA1）、O6-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）基因甲基化状态及其与临床病理特征的关系。方法　选取2015年1月—2016年6月海南医学院第二附属医院收治的符合纳入标准的乳腺癌患者100例为研究对象，采用甲基化特异性PCR法检测乳腺癌及癌旁组织中GSTP1、BRCA1、MGMT基因甲基化情况，并分析其与临床病理特征的关系，采用Cox回归分析分析GSTP1、BRCA1、MGMT基因甲基化状态与乳腺癌患者预后的关系。结果　乳腺癌组织中GSTP1、BRCA1、MGMT基因甲基化的发生率均高于癌旁组织（P<0.05）。每例患者乳腺癌组织甲基化基因数高于癌旁组织（P<0.05）。不同肿瘤分期、淋巴结转移情况的乳腺癌组织中甲基化基因数比较，差异有统计学意义（P<0.05）；癌组织直径≥20 mm、有淋巴结转移乳腺癌组织的GSTP1基因甲基化阳性率高于癌组织直径<20 mm、无淋巴结转移乳腺癌组织（P<0.05）；年龄<50岁、雌激素受体阴性乳腺癌组织BRCA1基因甲基化性阳率高于年龄≥50岁、雌激素受体阳性乳腺癌组织（P<0.05）；组织学Ⅲ级、乳腺癌Ⅱ~Ⅳ期、有淋巴结转移乳腺癌组织MGMT基因甲基化阳性率高于组织学Ⅰ~Ⅱ级、乳腺癌Ⅰ期、无淋巴结转移乳腺癌组织（P<0.05）。Cox回归分析结果显示，GSTP1、BRCA1、MGMT基因甲基化阳性是乳腺癌患者预后的影响因素（P<0.05）。结论　乳腺癌组织中GSTP1、BRCA1、MGMT基因甲基化基因数目高于高于癌旁组织，而且其异常甲基化与乳腺癌临床病理特征有关，能影响乳腺癌病情进展。

关键词: 乳腺肿瘤, 基因甲基化, 组织检测, 病理学