The prognostic significance of ERCC1, BRCA1, XRCC1, and beta 111-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection

Abstract

Objectives: The DNA repair pathway and isotype composition of beta-tubulin are known to be associated with resistance to platinum-and taxane-based chemotherapy, respectively. The aim of this study was to identify the clinical significance of excision repair cross-complementation 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), X-ray repair cross-complementation 1 (XRCC1) and beta III-tubulin on the chemotherapy response and overall survival in patients with non-small cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. Methods: Protein expression profiles were evaluated by immunohistochemistry on surgical specimens of 82 NSCLC patients who underwent platinum-and taxane-based neoadjuvant chemotherapy. The expression levels of proteins were measured semi-quantitatively and the correlation with tumor responses, pathologic cell death rate and survival were evaluated. Results: There were 73 (89.0%) clinical stage Ill patients. Lobectomy, bilobectomy, and pneumonectomy were performed in 54 (65.0%), 11(13.4%), and 17(20.7%) patients, respectively. There was no correlation between clinical response and protein expression. The expression levels of ERCC1, BRCA1, and XRCC1 increased proportionally to the cell death rate (p < 0.05): however, beta III-tubulin expression did not correlate with cell viability. Multivariate analysis demonstrated that early pathologic stage, adjuvant chemotherapy, high ERCC1 and low beta III-tubulin expression were good prognostic factors for overall survival (p < 0.05). Conclusions: The inverse correlation between DNA repair proteins and cell viability suggests that these protein expression levels can be markers for chemotherapy responsiveness. However, only ERCC1 and beta III-tubulin were prognostic factors after platinum-and taxane-based neoadjuvant chemotherapy following surgical resection. (C) 2009 Elsevier Ireland Ltd. All rights reserved.