HIF1α is an independent prognostic factor for overall survival in advanced primary epithelial ovarian cancer - a study of the OVCACAD 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 hypoxia-inducible factor-1 (HIF-1). The aim of this study was to investigate the impact of HIF1 alpha 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. HIF1 alpha expression was analyzed in tissue lysates, using an enzyme-linked immunosorbent assay. Results: HIF1 alpha was detected in 79.3% of the tissue samples. Patients with increased HIF1 alpha expression (cutoff: 80 pg/mg protein) in tumoral tissue lysates were more likely to have less favorable survival. HIF1 alpha (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: HIF1 alpha overexpression in ovarian cancer is associated with poor overall survival, underlining the importance of hypoxia in this angiogenesis driven disease.