Wen Xian-Feng, Shen Zan, Shen Zhen-Zhou, Nguyen Mai, Shao Zhi-Ming
Department of Surgery, Cancer Hospital/Cancer Institute, Fu Dan University, Shanghai 200032, P.R. China.
Oncol Rep. 2002 Sep-Oct;9(5):937-44.
Although cloning of ER beta has prompted a reevaluation of the role of ERs in human breast cancer and there have been many studies focusing on the clinical value of ER beta detection, however, few reports evaluated the prognostic significance of ER beta based on follow-up data. The VEGF gene transcription may be mediated by different ER subtypes directly. The aim of this study was to evaluate the relationship of angiogenesis factor VEGF with different ER subtypes and the prognostic value of ER beta and VEGF in 116 human breast cancer patients. Of these patients, 40 (34.5%) were ER beta protein high expressed and 76 (65.5%) were ER beta protein low expressed. When correlated the ER beta protein levels with other clinical characteristics, statistical significance (p<0.05) was found between ER beta protein expression and menopausal status, and tumor grade. No significance was found between ER beta protein level and node status, stage, or tumor size. Inverse relationship was found between ER beta protein expression and PR status (p<0.05). When comparing the VEGF levels with different ER subtypes a significant difference between ERs and VEGF was found. In ER beta protein high expression group, the VEGF protein was highly expressed (p<0.01), inverse relationship was also found between ER alpha and VEGF. In univariate analysis ER alpha, ER beta and VEGF levels had prognostic value for both relapse-free survival and overall survival (p<0.05). However, in a multivariate study, ER beta and ER alpha protein levels lost the prognostic value either to relapse-free survival or to overall survival. Only VEGF levels acted as an independent prognostic factor to disease-free survival. The result suggested that ER beta protein may have important prognostic value in human breast cancer patients. VEGF expression may be mediated through different ER subtypes.
尽管雌激素受体β(ERβ)的克隆促使人们重新评估雌激素受体(ERs)在人类乳腺癌中的作用,并且已有许多研究聚焦于ERβ检测的临床价值,然而,基于随访数据评估ERβ预后意义的报道却很少。血管内皮生长因子(VEGF)基因转录可能直接由不同的ER亚型介导。本研究旨在评估血管生成因子VEGF与不同ER亚型的关系,以及ERβ和VEGF在116例人类乳腺癌患者中的预后价值。在这些患者中,40例(34.5%)ERβ蛋白高表达,76例(65.5%)ERβ蛋白低表达。当将ERβ蛋白水平与其他临床特征进行关联分析时,发现ERβ蛋白表达与绝经状态和肿瘤分级之间具有统计学意义(p<0.05)。ERβ蛋白水平与淋巴结状态、分期或肿瘤大小之间未发现显著意义。ERβ蛋白表达与孕激素受体(PR)状态呈负相关(p<0.05)。当比较不同ER亚型的VEGF水平时,发现ERs与VEGF之间存在显著差异。在ERβ蛋白高表达组中,VEGF蛋白高表达(p<0.01),ERα与VEGF之间也呈负相关。单因素分析显示,ERα、ERβ和VEGF水平对无复发生存期和总生存期均具有预后价值(p<0.05)。然而,在多因素研究中,ERβ和ERα蛋白水平对无复发生存期或总生存期均失去了预后价值。只有VEGF水平是无病生存期的独立预后因素。结果表明,ERβ蛋白可能在人类乳腺癌患者中具有重要的预后价值。VEGF表达可能通过不同的ER亚型介导。