HIF1α is an independent prognostic factor for overall survival in advanced primary epithelial ovarian cancer – a study of the OVCAD Consortium

PURPOSE Hypoxia is a common phenomenon encountered in solid cancers, leading to chemotherapy resistance and therefore to aggressiveness of the disease. The homeostatic response to hypoxia is mediated by hypoxiainducible factor-1 (HIF-1). The aim of this study was to investigate the impact of HIF1α in patients with primary epithelial ovarian cancer. METHODS In this multicentric study, 275 patients with advanced primary epithelial ovarian cancer were included. All patients underwent cytoreductive surgery with maximal surgical effort and adjuvant platinum-based chemotherapy. HIF1α expression was analyzed in tissue lysates, using an enzyme-linked immunosorbent assay. RESULTS HIF1α was detected in 79.3% of the tissue samples. Patients with increased HIF1α expression (cutoff: 80 pg/mg protein) in tumoral tissue lysates were more likely to have less favorable survival. HIF1α (P=0.009, hazard ratio [HR] 2.505, 95% confidence interval [95% CI] 1.252-5.013) together with International Federation of Gynecology and Obstetrics (III versus IV) (P=0.013, HR 0.540, 95% CI 0.332-0.878), histology (P=0.007, HR 2.748, 95% CI 1.315-5.743), presence of peritoneal carcinomatosis (P=0.014, HR 2.176, 95% CI 1.170-4.046), residual tumor mass (P=0.017, HR 1.641, 95% CI 1.091-2.468), and response to platinum-based chemotherapy (P<0.001, HR 8.131, 95% CI 5.13-12.88) were independent prognosis factors for overall survival. The independent prognostic factors for progression-free survival were International Federation of Gynecology and Obstetrics stage (P=0.01), histological subtypes (P=0.016), and presence of peritoneal carcinomatosis (P<0.05). CONCLUSION HIF1α overexpression in ovarian cancer is associated with poor overall survival, underlining the importance of hypoxia in this angiogenesis driven disease.