Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy
Received 16 April 2009; received in revised form 27 July 2009; accepted 29 September 2009. published online 30 October 2009.
Abstract
Purpose
The aim of this study was to investigate prognostic value of multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP) and excision repair cross-complementing 1 (ERCC1) in patients with locally advanced non-small cell lung cancer (NSCLC) who received neoadjuvant cisplatin-based chemotherapy.
Methods
Transbronchial biopsy (TBB) specimens from 46 patients with stage IIIA (N2) NSCLC were collected to determine the expression level of MRP1, BCRP, LRP and ERCC1 mRNA by semiquantitative RT-PCR. The expression level of each gene was analyzed in relation to histopathologic response to chemotherapy, and tumor-free survival (TFS) and overall survival.
Results
Patients with MRP1 or LRP low expression had a significantly better histopathologic response (P=0.032 and 0.006), and a significantly longer TFS (P=0.043 and 0.025) and overall survival (P=0.019 and 0.013) than those with MRP1 or LRP high expression. Patients with ERCC1 low expression had a significantly longer overall survival (P=0.007), but not TFS (P=0.094) than those with ERCC1 high expression. In multivariate analysis, LRP low expression was a significantly favorable factor for TFS (P=0.027), and LRP and ERCC1 were significantly favorable factors for overall survival (P=0.012 and 0.032).
Conclusion
Assessment of MRP1 and LRP mRNA expression in TBB specimens may predict histopathologic response and survival in locally advanced NSCLC patients who received neoadjuvant cisplatin-based chemotherapy. ERCC1 expression was predictive for overall survival.
ABSTRACT