目的:探讨三阴性乳腺癌中DNMT1表达与ERα基因启动子甲基化的关系,以及二者在三阴性乳腺癌中的临床意义。方法:采用免疫组化法检测了126例三阴性乳腺癌组织中DNMT1蛋白的表达情况,同时采用甲基化特异性PCR法检测了ERα基因启动子区甲基化水平。结果:126例三阴性乳腺癌中,DNMT1阳性表达率为38.1%,ERα基因启动子区甲基化率为54.8%,DNMT1表达水平与ERα基因甲基化呈显著正相关(r=0.220,P=0.013)。与TNMⅠ-Ⅱ期组织相比,在TNMⅢ-Ⅳ期组织中ERα基因甲基化显著增加(P=0.040);与无淋巴结转移的组织相比,发生淋巴结转移的组织中DNMT1表达水平显著增加(P=0.043)。ERα基因启动子区甲基化与三阴性乳腺癌患者OS及DFS缩短显著相关(P=0.020,P=0.036);DNMT1阳性表达可显著缩短患者OS(P=0.034),同时可使患者DFS出现缩短趋势(P=0.054)。结论:三阴性乳腺癌中DNMT1蛋白参与了ERα基因甲基化,且该事件与三阴性乳腺癌的侵袭转移、病程进展及不良预后相关。
Objective:To investigate the relationship between DNMT1 expression and ERα gene promoter methylation and their clinical significance in triple - negative breast cancer (TNBC). Methods:The expression of DNMT1 protein was detected by immunohistochemical method, and the methylation level of ERα gene promoter was detected by methylation specific PCR method,in 126 cases of TNBC tissues. Results:In 126 cases of TNBC, the positive expression rate of DNMT1 was 38.1% , and the ERα gene promoter methylation rate was 54.8%. DNMTI expression level was significantly correlated with ERα gene promoter methylation ( r = 0. 220, P = 0. 013 ). Compared with TNM Ⅰ - Ⅱ stage, ERα was significantly increased in TNM Ⅲ- Ⅳ stage tissues (P = 0. 040) , and the expression level of DNMT1 was significantly increased in the tissues with lymph node metastasis (P = 0. 043). ERα gene promoter methylation was significantly associated with shorter OS and DFS(P = 0. 020, P = 0. 036) in patients with TNBC. DNMT1 positive expression was significantly associated with shorter OS (P = 0. 034) , and associated with a tendency of shorter DFS (P = 0. 054). Conclusion : DNMT1 is involved in the methylation of ERα gene in TNBC, and this event is associated with the invasion and metastasis of breast cancer,the progress and adverse prognosis of TNBC.