Azuma Koichi, Sasada Tetsuro, Kawahara Akihiko, Hattori Satoshi, Kinoshita Takashi, Takamori Sinzo, Ichiki Masao, Imamura Youhei, Ikeda Jiro, Kage Masayoshi, Kuwano Michihiko, Aizawa Hisamichi
Department of Internal Medicine, Division of Respirology, Neurology, and Rheumatology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Cancer Chemother Pharmacol. 2009 Aug;64(3):565-73. doi: 10.1007/s00280-008-0907-3. Epub 2009 Jan 3.
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.
In the present study, we evaluated whether ERCC1 and class III beta-tubulin expression could be used to predict progression-free and/or overall survival in 34 patients with locally advanced non-small cell lung cancer (NSCLC) receiving concurrent chemoradiation therapy with cisplatin and docetaxel, and immunohistochemistry was used to examine the expression of these two proteins in tumor samples obtained from the patients.
Immunostaining for ERCC1 and class III beta-tubulin was positive in 16 and 12 patients, respectively. A significant correlation was observed between ERCC1 expression and response to chemotherapy (P = 0.012), and between class III beta-tubulin expression and histology (P = 0.029). Patients negative for ERCC1 had a significantly longer median progression-free (62.5 vs. 36 weeks, P = 0.009), but not overall (171 vs. 50.5 weeks, P = 0.208), survival than those positive for ERCC1. Expression of class III beta-tubulin was not correlated with progression-free or overall survival (P = 0.563 and P = 0.265, respectively). Multivariate analysis adjusting for possible confounding factors showed that negative ERCC1 expression (hazard ratio = 3.972, P = 0.009) was a significantly favorable factor for progression-free survival.
This retrospective study indicates that immunostaining for ERCC1 may be useful for predicting survival in NSCLC patients receiving concurrent chemoradiotherapy with cisplatin and docetaxel, and can provide information critical for planning personalized chemotherapy.
据报道,切除修复交叉互补基因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。
在本研究中,我们评估了ERCC1和Ⅲ类β微管蛋白的表达是否可用于预测34例接受顺铂和多西他赛同步放化疗的局部晚期非小细胞肺癌(NSCLC)患者的无进展生存期和/或总生存期,并采用免疫组化法检测了从这些患者获取的肿瘤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16例和12例。观察到ERCC1表达与化疗反应之间存在显著相关性(P = 0.012),Ⅲ类β微管蛋白表达与组织学之间存在显著相关性(P = 0.029)。ERCC1阴性的患者中位无进展生存期显著更长(62.5周对36周,P = 0.009),但总生存期并非如此(171周对50.5周,P = 0.208),比ERCC1阳性的患者长。Ⅲ类β微管蛋白的表达与无进展生存期或总生存期均无相关性(分别为P = 0.563和P = 0.265)。对可能的混杂因素进行校正的多因素分析显示,ERCC1阴性表达(风险比 = 3.972,P = 0.009)是无进展生存期的显著有利因素。
这项回顾性研究表明,ERCC1免疫染色可能有助于预测接受顺铂和多西他赛同步放化疗的NSCLC患者的生存期,并可为制定个体化化疗方案提供关键信息。