title: HIF1α is an independent prognostic factor for overall survival in advanced primary epithelial ovarian cancer - a study of the OVCAD Consortium.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  HIF1α overexpression in ovarian cancer is associated with poor overall survival, underlining the importance of hypoxia in this angiogenesis driven disease.
authors.affiliation: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Elena Ioana
authors.initials: EI
authors.lastname: Braicu
authors.affiliation: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Luketina
authors.affiliation: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Richter
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Dan
authors.initials: D
authors.lastname: Cacsire Castillo-Tong
authors.affiliation: Department of Obstetrics and Gynecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Sandrina
authors.initials: S
authors.lastname: Lambrechts
authors.affiliation: Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Concin
authors.affiliation: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Mentze
authors.affiliation: Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria ; Ludwig Boltzmann Cluster Translational Oncology, General Hospital of Vienna, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.affiliation: Department of Obstetrics and Gynecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
keywords: HIF1α; platinum response; predictive factors; primary epithelial ovarian cancer; surgical outcome; survival