摘要目的 探讨不同类型乳腺组织中人runt相关转录因子3(Runx3)的蛋白表达及启动子甲基化的差异.方法 收集2010年2月至2012年8月间乳腺病变标本114例,包括纤维腺瘤35例、导管内癌39例、浸润性导管癌40例,选取浸润性导管癌的癌旁正常乳腺组织33例作为对照.免疫组织化学SP法检测Runx3蛋白在各类乳腺组织中的表达.高分辨率熔解曲线(HRM)分析各型组织中Runx3启动子甲基化程度.结果 Runx3蛋白主要表达于乳腺导管上皮细胞的细胞质.在正常乳腺组织、纤维腺瘤、导管内癌和浸润性导管癌中,Runx3蛋白的阳性率分别为87.9％ (29/33)、85.7％(30/35)、53.8％ (21/39)、40.0％ (16/40);而Runx3启动子甲基化率则分别为12.1％ (4/33)、20.0％(7/35)、46.2％ (18/39)、57.5％ (23/40).不同乳腺组织中Runx3启动子甲基化及其蛋白表达的相关性:正常乳腺组织、纤维腺瘤、导管内癌、浸润性导管癌组织中的r值分别为-0.431(P =0.012)、-0.408(P =0.015)、-0.589(P =0.000)、-0.743(P =0.000).结论 乳腺导管内癌和浸润性导管癌中Runx3蛋白的表达呈下降趋势,其启动子甲基化明显增高;Runx3基因启动子甲基化可能是乳腺癌发生发展的重要因素之一.

abstractsObjective To investigate the methylation status of Runx3 promoter and Runx3 expression in breast lesion tissues.Methods One hundred and fourteen breast lesions,including 35 cases of fibroadenoma,39 cases of intraductal carcinoma,40 cases of invasive ductal carcinoma,and 33 cases of normal breast tissue from Fabruary 2010 to August 2012 were included in this study.Runx3 protein expression was assessed by immunohistochemical SP method; whereas methylation of Runx3 promoter was assessed by high resolution melting (HRM) analysis.Results Runx3 protein was mainly expressed in the cytoplasm of ductal epithelial cells.The expression rates of Runx3 in normal breast tissue,fibroadenoma,ductal carcinoma in situ,invasive ductal carcinoma were 87.9％ (29/33),85.7％ (30/35),53.8％ (21/39),and 40.0％ (16/40) respectively.The methylation rates of Runx3 promoter were 12.1％ (4/33),20.0％ (7/35),46.2％ (18/39),and 57.5％ (23/40),respectively.Correlation analysis between promoter methylation and protein expression of Runx3 in different breast tissue showed the r value in normal breast tissue,fibroadenoma,ductal carcinoma in situ and invasive ductal carcinoma was-0.431 (P =0.012),-0.408 (P =0.015),-0.589 (P =0.000) and-0.743 (P =0.000) respectively.Conclusions Runx3 protein expression shows a downward trend in ductal carcinoma in situ and invasive ductal carcinoma,meanwhile its promoter methylation increases significantly.The methylation of Runx3 promoter may be one of the important factors in the occurrence and development of breast cancer.