ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer.
The excision repair cross-complementation group 1 (ERCC1) and BRCA1 have been identified as predictors of clinical outcomes among patients with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. In this study, we immunohistochemically examined the ERCC1 and BRCA1 protein expression levels in 35 patients with metastatic mediastinal lymph nodes obtained prior to treatment as retrospective study. These patients had been enrolled in our studies on neoadjuvant chemotherapy with cisplatin and irinotecan (15 patients) or chemoradiotherapy with cisplatin and docetaxel plus concurrent thoracic radiation (20 patients). The relations between the ERCC1 or BRCA1 protein expression and the clinical outcomes of the patients were then examined. The rates of radiological response and pathological effectiveness were significantly higher among patients with ERCC1-negative tumors, compared with those with positive tumors in the neoadjuvant chemotherapy group (radiological response rates; 100% vs. 42.8%, P=0.013; pathological effectiveness; 100% vs. 47.1%, P=0.038), but no associations were observed in the neoadjuvant chemoradiotherapy group. Regarding survival, no significant differences in overall survival or disease-free survival were observed between patients with ERCC1-negative and positive tumors in both the neoadjuvant chemotherapy and chemoradiotherapy groups. In summary, we showed that a ERCC1-negative protein status was significantly related to tumor responsiveness to neoadjuvant chemotherapy with cisplatin and irinotecan, but such a status was not a clear prognostic predictor to cisplatin-based neoadjuvant therapy in NSCLC patients. Further study is needed to clarify the value of molecular predictors for customizing therapy for patients with NSCLC.
Fujii
Tetsuya
T
Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Toyooka
Shinichi
S
Ichimura
Kouichi
K
Fujiwara
Yoshiro
Y
Hotta
Katsuyuki
K
Soh
Junichi
J
Suehisa
Hiroshi
H
Kobayashi
Naruyuki
N
Aoe
Motoi
M
Yoshino
Tadashi
T
Kiura
Katsuyuki
K
Date
Hiroshi
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000378:metabolism*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000077143:Docetaxel; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004268:DNA-Binding Proteins; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D002166:Camptothecin