Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Mod Pathol. 2011 Mar;24(3):453-62. doi: 10.1038/modpathol.2010.211. Epub 2010 Nov 19.
Assessment of estrogen receptor (ER) expression by immunohistochemistry has yielded inconsistent results as a prognostic indicator in ovarian carcinoma. In breast and endometrial carcinomas, panels of estrogen-induced genes have shown improved prognostic capability over the use of ER immunohistochemistry alone. For both breast and endometrial cancers, overexpression of estrogen-induced genes is associated with better prognosis. We hypothesized that analysis of a panel of estrogen-induced genes can predict the outcome in ovarian carcinoma and potentially differentiate between tumors of varying hormonal responsiveness. From a cohort of 219 women undergoing ovarian cancer surgery from 2004 to 2007, 83 patients were selected for inclusion. All patients had advanced stage ovarian/primary peritoneal high-grade serous carcinoma and underwent primary surgical debulking, followed by adjuvant treatment with platinum and taxane agents. The expression of ERα and six genes known to be induced by estrogen in the female reproductive tract (namely EIG121, sFRP1, sFRP4, RALDH2, PR, and IGF-1) was measured using quantitative RT-PCR. Unsupervised cluster analyses were used to categorize patients as high or low gene expressors. Gene expression results were then compared with those for ER immunohistochemistry. Clusters were compared using χ(2) analyses, and Cox proportional hazards models were used to evaluate survival outcomes. The median follow-up time was 38.7 months (range: 1-68). A cluster defined by EIG121 and ERα segregated tumors into distinct groups of high and low gene expressors. Shorter overall survival (OS) was associated with high gene expression (HR 2.84 (1.11-7.30), P=0.03), even after adjustment for other covariates. No difference in ER immunohistochemistry expression was noted between gene clusters. In contrast to other hormonally driven cancers, high expression of ERα and the estrogen-induced gene EIG121 predicts shorter OS in patients with high-grade serous ovarian carcinoma. Such a biomarker panel may potentially be used to guide management with estrogen antagonists in this patient population.
免疫组织化学评估雌激素受体 (ER) 的表达作为卵巢癌的预后指标，结果并不一致。在乳腺癌和子宫内膜癌中，雌激素诱导基因的组合已显示出比单独使用 ER 免疫组织化学更好的预后能力。对于乳腺癌和子宫内膜癌，雌激素诱导基因的过度表达与更好的预后相关。我们假设分析一组雌激素诱导基因可以预测卵巢癌的结局，并可能区分不同激素反应性的肿瘤。在 2004 年至 2007 年接受卵巢癌手术的 219 名女性队列中，选择了 83 名患者进行纳入。所有患者均患有晚期卵巢/原发性腹膜高级别浆液性癌，并接受了原发性手术去瘤，随后接受铂类和紫杉烷类药物辅助治疗。使用定量 RT-PCR 测量 ERα 和女性生殖道中已知受雌激素诱导的六个基因 (即 EIG121、sFRP1、sFRP4、RALDH2、PR 和 IGF-1) 的表达。使用无监督聚类分析将患者分为高或低基因表达者。然后将基因表达结果与 ER 免疫组织化学结果进行比较。使用 χ(2)分析比较聚类，使用 Cox 比例风险模型评估生存结果。中位随访时间为 38.7 个月（范围：1-68）。由 EIG121 和 ERα 定义的聚类将肿瘤分为高和低基因表达者的不同组。高基因表达与总生存期 (OS) 更短相关（HR 2.84 (1.11-7.30)，P=0.03），即使在调整其他协变量后也是如此。基因簇之间未观察到 ER 免疫组织化学表达的差异。与其他激素驱动的癌症相反，高级别浆液性卵巢癌患者中 ERα 和雌激素诱导基因 EIG121 的高表达预测 OS 更短。这种生物标志物组合可能有可能用于指导该患者群体的雌激素拮抗剂管理。
