Suzuki Takashi, Urano Tomohiko, Tsukui Tohru, Horie-Inoue Kuniko, Moriya Takuya, Ishida Takanori, Muramatsu Masami, Ouchi Yasuyoshi, Sasano Hironobu, Inoue Satoshi
Department of Pathology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi-ken, Japan.
Clin Cancer Res. 2005 Sep 1;11(17):6148-54. doi: 10.1158/1078-0432.CCR-05-0040.
Estrogen-responsive finger protein (Efp) is a member of RING finger-B box-Coiled Coil family and is also a downstream target of estrogen receptor alpha. Previously, Efp was shown to mediate estrogen-induced cell growth, which suggests possible involvement in the development of human breast carcinomas. In this study, we examined expression of Efp in breast carcinoma tissues and correlated these findings with various clinicopathologic variables.
Thirty frozen specimens of breast carcinomas were used for immunohistochemistry and laser capture microdissection/real-time PCR of Efp. Immunohistochemistry for Efp was also done in 151 breast carcinoma specimens fixed with formalin and embedded in paraffin wax.
Efp immunoreactivity was detected in breast carcinoma cells and was significantly associated with the mRNA level (n = 30). Efp immunoreactivity was positively associated with lymph node status or estrogen receptor alpha status and negatively correlated with histologic grade or 14-3-3sigma immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlated with poor prognosis of breast cancer patients, and multivariate analyses of disease-free survival and overall survival for 151 breast cancer patients showed that Efp immunoreactivity was the independent marker.
Our data suggest that Efp immunoreactivity is a significant prognostic factor in breast cancer patients. These findings may account for an oncogenic role of Efp in the tumor progression of breast carcinoma.
雌激素反应性指蛋白(Efp)是指环指-B盒-卷曲螺旋家族的成员,也是雌激素受体α的下游靶点。此前研究表明,Efp可介导雌激素诱导的细胞生长,提示其可能参与人类乳腺癌的发生发展。在本研究中,我们检测了Efp在乳腺癌组织中的表达,并将这些结果与各种临床病理变量进行关联分析。
30例乳腺癌冷冻标本用于Efp的免疫组织化学检测以及激光捕获显微切割/实时定量PCR分析。同时,对151例经福尔马林固定、石蜡包埋的乳腺癌标本进行Efp免疫组织化学检测。
在乳腺癌细胞中检测到Efp免疫反应性,且其与mRNA水平显著相关(n = 30)。Efp免疫反应性与淋巴结状态或雌激素受体α状态呈正相关,与组织学分级或14-3-3σ免疫反应性呈负相关(n = 151)。此外,Efp免疫反应性与乳腺癌患者的不良预后显著相关,对151例乳腺癌患者的无病生存期和总生存期进行多因素分析显示,Efp免疫反应性是独立的预后标志物。
我们的数据表明,Efp免疫反应性是乳腺癌患者的一个重要预后因素。这些发现可能解释了Efp在乳腺癌肿瘤进展中的致癌作用。