BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer
BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer
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DOI：
10.1016/j.ygyno.2011.08.017
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发表时间：
2011-12-01
影响因子：
4.7
通讯作者：
Harkin, D. Paul
中科院分区：
文献类型：
--
作者：
Carser, Judith E.;Quinn, Jennifer E.;Harkin, D. Paul
目标.我们通过免疫组化（IHC）研究了散发性卵巢上皮癌（EOC）患者接受铂类和铂类/紫杉烷化疗后BRCA 1蛋白表达与临床结局的关系。BRCA 1免疫组化对来自两个英国肿瘤中心的292例卵巢肿瘤进行了研究。多因素分析显示BRCA 1蛋白表达水平与总生存期（OS）、无进展生存期（PFS）及化疗疗效相关。与BRCA 1高表达患者相比，BRCA 1蛋白表达缺失/低表达的EOC患者（41%）在化疗后有更好的临床反应机会（比值比2.47：95%CI 1.10-5.55，p = 0.029）。与BRCA 1高表达患者相比，BRCA 1缺失/低表达患者接受单药铂类治疗后临床应答的概率更高（68.5% vs. 46.8%），而添加紫杉烷可增加应答率，与BRCA 1无关。总体而言，BRCA 1缺失/低表达患者的OS（HR =0.65：95%CI 0.48-0.88，p = 0.006）和PFS（HR = 0.74，95%CI 0.55-0.98，p = 0.040）均优于BRCA 1蛋白高表达患者。我们证实，BRCA 1蛋白表达缺失/低表达是一个有利的预后标志物。然而，我们也提供了第一个证据表明，在散发性EOC患者中，BRCA 1蛋白表达缺失/低表达预示着对化疗的临床反应改善。(C)2011 Elsevier Inc. All rights reserved.
Objectives. We investigated the relationship between BRCA1 protein expression by immunohistochemistry (IHC) and clinical outcome following platinum and platinum/taxane chemotherapy in sporadic epithelial ovarian cancer (EOC).Methods. BRCA1 IHC was performed on a cohort of 292 ovarian tumours from two UK oncology centres. BRCA1 protein expression levels were correlated with overall survival (OS), progression free survival (PFS) and clinical response to chemotherapy by multivariate analysis.Results. EOC patients with absent/low BRCA1 protein expression (41%) had a better chance of clinical response following chemotherapy as compared to patients with high BRCA1 expression (odds ratio 2.47: 95%CI 1.10-5.55, p = 0.029). Patients with absent/low BRCA1 had a higher probability of clinical response following single agent platinum compared to high BRCA1 expressing patients (68.5% vs. 46.8%), while addition of a taxane increased response rates independent of BRCA1. Overall, patients with absent/low BRCA1 had a better clinical outcome compared to patients with high BRCA1 protein expression in terms of both OS (HR =0.65: 95%CI 0.48-0.88, p = 0.006) and PFS (HR = 0.74, 95%CI 0.55-0.98, p = 0.040).Conclusions. We confirm that absent/low BRCA1 protein expression is a favourable prognostic marker. However, we also provide the first evidence that absent/low BRCA1 protein expression in sporadic EOC patients predicts for an improved clinical response to chemotherapy. (C) 2011 Elsevier Inc. All rights reserved.