Expression of ERCC1 and class III β-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxel

Expression of ERCC1 and class III β-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxel
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DOI:
10.1016/j.lungcan.2008.09.002
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发表时间:
2009-06-01
期刊:
影响因子:
5.3
通讯作者:
Aizawa, Hisamichi
Aizawa, Hisamichi
中科院分区:
医学2区
文献类型:
--
作者:
Azuma, Koichi;Sasada, Tetsuro;Aizawa, Hisamichi

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卡铂联合紫杉醇是治疗晚期非小细胞肺癌(NSCLC)患者最常用的方案。据报道,切除修复交叉互补组1(ERCC 1)的表达与铂类药物的耐药性相关。据报道,III类β-微管蛋白与对紫杉烷类的耐药性相关。我们评估了ERCC 1和III类β-微管蛋白表达是否可以预测接受卡铂和紫杉醇治疗的复发性NSCLC患者的无进展生存期和/或总生存期。免疫组织化学方法检测了45例经卡铂和紫杉醇治疗的肺癌患者切除肿瘤标本中这两种蛋白的表达。ERCC 1和III类β-微管蛋白的免疫染色分别在20例和16例患者中呈阳性。与ERCC 1阳性患者相比,ERCC 1阴性患者的中位无进展生存期(44周vs. 28周,P=0.046)和总生存期(102周vs. 56周,P=0.010)显著延长。与III类β-微管蛋白表达阳性的患者相比,III类β-微管蛋白表达阴性的患者的中位无进展生存期(40周vs. 35周,P=0.031)显著更长,但总体生存期(78周vs. 57周,P=0.087)并非如此。特别是,与ERCC 1和/或III类β-微管蛋白阳性患者相比,ERCC 1和III类β-微管蛋白阴性患者的无进展生存期(P =0.036)和总生存期(P=0.015)显著延长。在多因素分析中,III类β-微管蛋白阴性表达(风险比= 1.912,P=0.048)是无进展生存期的显著有利因素,ERCC 1阴性表达(风险比= 2.580,P=0.014)和较好的体力状态(风险比= 3.287,P=0.007)是总生存期的显著有利因素。这项回顾性研究表明,ERCC 1和III类β-微管蛋白的免疫染色可能有助于预测接受卡铂和紫杉醇治疗的NSCLC患者在根治性切除术后复发肿瘤的生存率,并可为计划个性化化疗提供关键信息。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
The combination of carboplatin and paclitaxel is the most commonly used regimen for the treatment of advanced non-small cell lung cancer (NSCLC) patients. The expression of excision repair cross-complementation group 1 (ERCC1) is reported to be correlated with resistance to platinum-based drugs. Class III beta-tubulin is reported to be correlated with resistance to taxanes. We evaluated whether ERCC1 and class III beta-tubulin expression could predict progression-free and/or overall survival in relapsed NSCLC patients treated with carboplatin and paclitaxel. Immunohistochemistry was used to examine the expression of these two proteins in resected lung tumor samples obtained from 45 patients treated with carboplatin and paclitaxel against recurrent tumors after curative resection. Immunostaining for ERCC1 and class III beta-tubulin was positive in 20 and 16 patients, respectively. Patients negative for ERCC1 had a significantly longer median p rogression-free (44 weeks vs. 28 weeks, P=0.046) and overall (102 weeks vs. 56 weeks, P=0.010) survival than those positive for ERCC1. Patients negative for class III P-tubulin expression had a significantly longer median progression-free (40 weeks vs. 35 weeks, P=0.031), but not overall (78 weeks vs. 57 weeks, P=0.087), survival than those positive for class III beta-tubulin expression. In particular, patients negative for both ERCC1 and class III beta-tubulin had significantly longer progression-free (P=0.036) and overall survival (P=0.015), compared with those positive for ERCC1 and/or class III beta-tubulin. In multivariate analysis, negative class III beta-tubulin expression (hazard ratio = 1.912, P=0.048) was significantly favorable factor for progression-free survival, and negative ERCC1 expression (hazard ratio = 2.580, P=0.014) and better performance status (hazard ratio = 3.287, P=0.007) were significantly favorable factors for overall survival. This retrospective study indicates that immunostaining for ERCC1 and class III beta-tubulin may be useful for predicting survival in NSCLC patients receiving carboplatin and paclitaxel against recurrent tumors after curative resection and can provide information critical for planning personalized chemotherapy. (C) 2008 Elsevier Ireland Ltd. All rights reserved.