Expression of ERCC1 and class III beta-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxel.
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.
Azuma
Koichi
K
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. azuma@med.kurume-u.ac.jp
Sasada
Tetsuro
T
Kawahara
Akihiko
A
Takamori
Sinzo
S
Hattori
Satoshi
S
Ikeda
Jiro
J
Itoh
Kyogo
K
Yamada
Akira
A
Kage
Masayoshi
M
Kuwano
Michihiko
M
Aizawa
Hisamichi
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C498585:TUBB3 protein, human; D014404:Tubulin; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel