Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples
Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples
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DOI：
10.1016/j.ygyno.2003.11.053
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发表时间：
2004-04-01
影响因子：
4.7
通讯作者：
Seiden, MV
中科院分区：
文献类型：
--
作者：
Penson, RT;Oliva, E;Seiden, MV
目标。MDRI在紫杉醇临床耐药中的作用尚不清楚。本研究旨在确定P-糖蛋白(P-gp)过表达与卵巢癌患者生存、肿瘤对紫杉醇的反应以及先前细胞毒暴露对P-gp表达的影响。回顾性生存分析。免疫组织化学方法检测P-gp的表达。从肿瘤登记中确定了32名患者。一次手术和二次手术之间的中位间隔为17.9(5.7-40.9)个月。仅5例原发肿瘤(16%)P-gp染色阳性。一线治疗含紫杉醇17例(53%)，26例(8.1%)在二次手术前接受过P-gp可输出化疗。仅7例(22%)复发肿瘤为+。7例紫杉醇++或+复发者中仅1例有效(14%(95%CI 0~46%))，而10例0/+复发者中有8例有效(80%(CI 46~100%)，P=0.025)。在二次手术后预后的多因素分析中，对紫杉醇的反应(P=0.004)和P-gp的过度表达(P<；0.001)是显著的生存预测因素。新生的强P-gp过度表达并不常见，随着时间的推移或先前接受化疗的患者似乎变化不大。然而，P-gp的过度表达是一个重要的预后因素，在疾病发生时，复发与肿瘤对紫杉醇的反应呈负相关。(C)2004 Elsevier Inc.保留所有权利。
Objective. The role of MDRI in clinical paclitaxel resistance remains poorly characterized. This study sought to identify the incidence and significance of P-glycoprotein (P-gp) over-expression on Survival, tumor response to paclitaxel and the effect of prior cytotoxic exposure on P-gp expression in patients with paired primary and recurrent ovarian cancer samples.Methods. Retrospective survival analysis. P-gp expression was evaluated immunohistochemically with antibodies c494 and c219.Results. Thirty-two patients were identified from the tumor registry. Median interval between primary and secondary surgery was 17.9 (5.7-40.9) months. Only five primary tumors (16%) demonstrated +++ staining for P-gp. First-line treatment contained paclitaxel in 17 patients (53%) and 26 patients (8 1%) had been exposed to P-gp exportable chemotherapy before second surgery. Only seven of the recurrent tumors (22%) were +++. Only one of seven (14% (95% CI 0-46%)) recurrent tumors with ++ or +++ staining responded to subsequent paclitaxel, while 8 of 10 (80% (CI 46-100%)) recurrent tumors with 0/+ staining responded (P= 0.025). In multivariate analysis of outcome following second surgery, response to paclitaxel (P= 0.004) and P-gp over-expression (P < 0.001) were significant predictors of survival.Conclusions. De novo strong P-gp over-expression is uncommon, appears to change little over time or with prior exposure to chemotherapy. However, P-gp over-expression is a significant prognostic factor, and at the time of disease, relapse is inversely correlated with tumor response to paclitaxel. (C) 2004 Elsevier Inc. All rights reserved.