Excision repair cross complementing-1 and topoisomerase IIα gene expression in small-cell lung cancer patients treated with platinum and etoposide -: A retrospective study

Hypothesis: Aim of the study was to quantify ERCC 1, RRM 1, and TopoII alpha mRNA expression profile as predictive factors for response and survival in SCLC patients treated with platinum/etoposide. Methods: Total RNA was extracted from microdissected sections of 103 formalin-fixed, paraffin embedded biopsies. Relative quantification was performed by real-time polymerase chain reaction (PCR) using intron-spanning probes. Results: Eighty-five samples (83%) were successfully amplified. Median overall survival (OS) was 9.9 months; 45 patients had limited disease (LD) (OS = 13. 1) and 40 had extensive disease (ED) (OS = 7.1). Fifty-six (65%) patients had an objective response to treatment. A gene expression was detectable in all samples and a correlation between ERCC1 and RRM 1 (R-s = 0.34, p = 0.00 11) was found. According to response to treatment, it was found that lower TopoII alpha expression was associated to a better response in LD patients (p = 0.025) and, more interestingly, those who had a complete response had lower TopoII alpha than both partial and nonresponsive patients (p = 0.015). At univariate analysis LD patients with low ERCC I had significantly longer survival (median survival 14.9 versus 9.9, p = 0.012), whereas RRM1 and TopoII alpha levels showed no influence on Outcome. At the multivariate analysis, ERCC1 was confirmed to be an independent prognostic factor for survival in LD patients. No significant role was found for ERCC1, RRM I and TopoII alpha in ED patients. Conclusions: ERCC1 and TopoII alpha are candidate markers in predicting clinical outcome and response to treatment in LD SCLC patients and are worth of further investigation in a prospective study.