Hypoxia-Inducible Factor-1 alpha and Excision Repair Cross-Complementing 1 in Patients with Small Cell Lung Cancer Who Received Front-Line Platinum-Based Chemotherapy A Retrospective Study

Abstract

Introduction: Hypoxia-inducible factor-1 alpha (HIF-1 alpha), which plays an essential role in the adaptive response of cells to hypoxia, is associated with aggressive tumor behavior. Furthermore, a relationship between excision repair cross-complementing 1 (ERCC1) expression and platinum resistance has been reported in patients with various malignancies. The aim of this study was to investigate the expression of HIF-1 alpha and ERCC1 and to elucidate the clinical significance of their expression in patients with small cell lung cancer (SCLC) treated with front-line platinum-based chemotherapy. Methods: SCLC biopsy samples were obtained before front-line platinum-based chemotherapy from 111 patients with SCLC (limited disease, 29; extensive disease [ED], 82) between January 2002 and December 2009 at Gyeongsang National University Hospital. The expression levels of HIF-1 alpha and ERCC1 were assessed by immunohistochemistry. Results: High expression levels of ERCC1 and HIF-1 alpha were observed in 49 (44.1%) and 71 (64.0%) of 111 patients, respectively. Expression of ERCC1 and HIF-1 alpha was not significantly associated with age, sex, Eastern Cooperative Oncology Group performance status, weight loss, or response to treatment, regardless of stage. In ED-SCLC, low expression in the HIF-1 alpha group showed statistically better survival compared with high expression in the HIF-1 alpha group (p = 0.018). Multivariate analysis revealed that response to front-line platinum-based chemotherapy (p < 0.001), good Eastern Cooperative Oncology Group performance status (0-1) (p = 0.002), and low expression of HIF-1 alpha (p = 0.004) were independent predictors of better overall survival in ED-SCLC. Conclusions: Low expression of HIF-1 alpha may be a useful predictor of better overall survival in ED-SCLC patients treated with front-line platinum-based chemotherapy.