Prognostic and/or predictive value of ERCC1, BRCA1, ATP7B, TOPO1, TOPO2A, and TOPO2B genes in patients with small cell lung cancer (SCLC).

Abstract

e21049 Background: The aim of the study was to evaluate the possible prognostic and predictive value of genes’ expression correlated with cisplatin-etoposide (EP) metabolism or mode of function (ERCCI, BRCA1, ATP7B, TOPOI, TOPOIIA, and TOPOIIB) in patients with SCLC. We report here the results of the experimental arm of the study. Methods: Tumor samples from 114 patients, with SCLC have been analyzed for ERCCI, BRCA1, ATP7B, TOPOI, TOPOIIA, and TOPOIIB mRNA expression by quantitative real-time PCR, from microdissected cells derived from patients’ primary tumors. Consecutive patients with SCLC and available tumor tissue for genomic analysis were included in the study. All patients were treated with EP (plus radiotherapy for patients with limited disease) in the department of Medical Oncology of the University Hospital of Heraklion. Results: The median age of the patients was 62 years (min-max: 33-85). Seventy-five (66%) patients presented with extended disease, LDH was above the upper normal limits in 68 (60%) of the patients while ECOG performance status was 0-1 in 100 (90%) of them. High ERCC1 and BRCA1 mRNA levels were associated with elevated LDH (p=0.03 and p=0.039, respectively). In addition high ERCC1 expression was correlated with PS 2 (p=0.02) while a statistical trend was found for high BRCA1 expression and deteriorated PS (p=0.09). High ERCC1 and BRCA1 expression was correlated with significant decreased time to tumor progression (TTP; p=0.035 and 0.026 respectively). A non significant statistical trend (p=0.1) was observed for decreased median overall survival (mOS) in patients with high ERCC1 expression. No correlation was found for other analyzed genes with clinical parameters. Conclusions: These data indicate for the first time that the ERCC1-BRCA1 mRNA expression in the primary tumor at the time of diagnosis could be used for the prediction of platinum resistance in patients with SCLC. The results of this study will be validated in an independent cohort of patients with similar characteristics.