三阴性乳腺癌患者中FOXA1与雌激素受体β的表达及其相关性研究

The expression and relationship between FOXA1 and ERβ in triple negative breast cancer

背景与目的:研究显示雌激素受体β(estrogen receptor beta,ERβ)在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达与TNBC患者的预后可能存在正相关,而ERβ和雌激素受体α(estrogen receptor alpha,ERα)存在高度同源性,ERα的表达和活性与叉头框蛋白A1(fork head box protein A1,FOXA1)密切相关。该研究旨在分析FOXA1和ERβ在TNBC中的表达情况及其与临床病理指标及预后的相关性。方法:收集2011年11月—2013年12月北京协和医院乳腺癌标本,根据ERα、孕激素受体(progesterone receptor,PR)和人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)的表达情况,筛选出TNBC。根据ERβ表达,随机选取ERβ阳性和阴性的乳腺癌标本各30例,应用免疫组化检测样本中FOXA1表达情况。由于染色不佳及飞片等原因,最终获得染色情况佳的标本共48例(ERβ阴性20例,ERβ阳性28例)。比较TNBC中FOXA1及ERβ表达的相关性及其与各临床病理指标及预后之间的关系。结果:FOXA1总体阳性率为35.4%(17/48),其中ERβ阳性组FOXA1阳性率为35.7%(10/28),ERβ阴性组FOXA1阳性率为35%(7/20),两组差异无统计学意义(P=0.83),即FOXA1的表达与ERβ的表达无相关性。FOXA1阳性组与FOXA1阴性组的患者年龄、肿瘤大小、腋窝淋巴结转移数目、肿瘤分级、肿瘤分期、诺丁汉预后指数(Nottingham prognostic index,NPI)和无病生存率(disease free survival,DFS)差异均无统计学意义;两组Ki-67指数差异具有统计学意义(P<0.01),即在FOXA1阳性组中Ki-67指数显著低于FOXA1阴性组,两者呈负相关。结论:在TNBC中,FOXA1的表达与ERβ的表达差异无统计学意义,FOXA1的表达与Ki-67指数呈负相关,提示FOXA1阳性表达的三阴性乳腺癌细胞增殖性较低。

Background and purpose： The expression of ERβ in triple negative breast cancer（TNBC） might be associated with good prognosis in TNBC patients. ERβ and ERct have considerable homology. FOXA1 plays an important role in ERa expression and function. The aim of this study was to analyze the expression of FOXA1 and ERβ in TNBC and the relationship between them and the clinicopathologic characteristics and prognosis. Methods： The breast cancer samples in Peking Union Medical College Hospital were collected from Nov. in 2011 to Dec. in 2013, and TNBC were screened out based on the expression of ERa, PR and HER-2. Thirty ERβ-negative samples and 30 ERβ- positive samples were selected randomly according to the ERβ expression. We used immunohistochemical method to detect the expression of FOXA1. Finally, 48 TNBC samples were obtained to analyze the results. Results： The total positive rate of FOXA 1 was 35.4% （17/48）. In the ERβ-positive group, the positive rate of FOXA 1 was 35.7% （10/28）,and in the ERI3-negative group, the positive rate of FOXA1 was 35% （7/20）. The expression of FOXA1 in these 2 groups had no significant difference （P=0.83）, which indicated that there was no relation between ERβ and FOXA1. The FOXA1 positive group and FOXA1 negative group also showed no significant difference in age, tumor size, and lymphatic metastasis number in axilla, tumor grade, tumor stage, NPI and DFS. However, Ki-67 showed negative correlation with FOXA1 expression （P〈0.01）. Conclusion： FOXA1 expression had no relationship with ERβ expression in TNBC. Ki-67 showed negative correlation with FOXA1 expression, which might hint that the proliferation of tumor cell was lower in FOXA1 positive TNBC.