Azuma Koichi, Sasada Tetsuro, Kawahara Akihiko, Takamori Sinzo, Hattori Satoshi, Ikeda Jiro, Itoh Kyogo, Yamada Akira, Kage Masayoshi, Kuwano Michihiko, Aizawa Hisamichi
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Lung Cancer. 2009 Jun;64(3):326-33. doi: 10.1016/j.lungcan.2008.09.002. Epub 2008 Nov 1.
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 progression-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 beta-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.
卡铂与紫杉醇联合使用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（ERCC1）的表达与铂类药物耐药相关。据报道，III类β微管蛋白与紫杉烷类耐药相关。我们评估了ERCC1和III类β微管蛋白的表达是否能预测接受卡铂和紫杉醇治疗的复发NSCLC患者的无进展生存期和/或总生存期。采用免疫组织化学法检测45例接受卡铂和紫杉醇治疗的根治性切除术后复发性肿瘤患者的肺肿瘤切除样本中这两种蛋白的表达。ERCC1和III类β微管蛋白免疫染色阳性的患者分别为20例和16例。ERCC1阴性的患者中位无进展生存期（44周对28周，P = 0.046）和总生存期（102周对56周，P = 0.010）显著长于ERCC1阳性的患者。III类β微管蛋白表达阴性的患者中位无进展生存期（40周对35周，P = 0.031）显著长于III类β微管蛋白表达阳性的患者，但总生存期（78周对57周，P = 0.087）无显著差异。特别是，与ERCC1和/或III类β微管蛋白阳性的患者相比，ERCC1和III类β微管蛋白均阴性的患者无进展生存期（P = 0.036）和总生存期（P = 0.015）显著更长。在多变量分析中，III类β微管蛋白表达阴性（风险比=1.912，P = 0.048）是无进展生存期的显著有利因素，ERCC1表达阴性（风险比=2.580，P = 0.014）和更好的体能状态（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，ERCC1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根治性切除术后复发性肿瘤的NSCLC患者的生存期，并可为制定个性化化疗提供关键信息。
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