乳腺浸润性导管癌中CDH1基因甲基化状态及其临床意义

摘要

目的 探讨CDH1启动子基因甲基化在乳腺浸润性导管癌中的意义.方法 采用甲基特异性PCR和免疫组织化学染色方法分别检测乳腺癌组织、癌旁组织和乳腺正常组织中CDH1基因启动子甲基化状况及上皮型钙黏蛋白(E-cadherin)表达情况.收集相关临床病理资料(遗传背景、年龄、肿瘤大小、腋窝淋巴结转移情况、肿瘤细胞分级、临床分期和分子亚型),分析CDH1基因甲基化在乳腺癌中的意义.结果 250例乳腺癌患者共发现113例CDH1基因启动子甲基化,甲基化率为45.20％,CDH1基因启动子甲基化组和非甲基化组相比E-cadherin蛋白表达水平明显减低,差异有统计学意义(x2 =21.360,P＜0.01).单因素分析结果显示,CDH1基因甲基化组和非甲基化组在腋窝淋巴结转移(x2=19.086,P＜0.01)、肿瘤组织学分级(x2=8.487,P=0.014)、人表皮生长因子受体2(CerbB-2)表达(x2=9.475,P=0.002)和分子分型(x2 =25.482,P＜0.01)比较,差异有统计学意义.COX回归分析显示,CDH1基因启动子甲基化和非甲基化组5年生存率比较,差异有统计学意义(P＜0.01).结论 CDH1基因启动子甲基化引起基因mRNA表达下降,CDH1基因甲基化与乳腺癌的腋窝淋巴结转移相关,提示CDH1基因启动子甲基化在乳腺癌疾病进程中发挥了一定作用.%Objective To explore the significance of gene promoter methylation of CDH1 in breast invasive ductal carcinoma.Methods The gene promoter methylation of CDH1 and E-cadherin expression status in breast cancer tissues,adjacent tissues and normal breast tissues were detected by using methylation specific polymerase chain reaction (PCR) and immunohistochemistry (SP) method.The clinicopathological data (genetic background,age,tumor size,axillary lymph node metastasis,tumor cells grading,clinical staging and molecular subtype) were collected,and analysed the clinical significance of gene promoter methylation of CDH1 in breast cancer.Results Among the 250 patients with breast cancer,113 cases were found gene promoter methylation of CDH1,and the methylation rate was 45.20％.Compared with patients with unmethylated CDH1 gene promoter,the E-cadherin protein expression was reduced in patients with methylated CDH1 gene promoter,there was statistically significant difference (x2 =21.360,P＜0.01).The univariate analysis showed that statistically significant differences were found in axillary lymph node metastasis (x2=19.086,P＜0.01),histological grading of tumor (x2 =8.487,P=0.014),CerbB-2 expression (x2=9.475,P=0.002) and molecular typing (x2 =25.482,P＜0.01) between patients with methylated and unmethylated CDH1 gene promoter.The COX regression analysis showed that there was significant difference in 5-year survival rate between patients with methylated and unmethylated CDH1 gene promoter(P＜0.01).Conclusion Methylation of CDH1 gene promoter causes decreasedexpression of mRNA,and is associated with axillary lymph node metastasis in breast cancer,which suggests that methylation of CDH1 gene promoter plays a certain role in breast cancer progression.