Back to Journals » OncoTargets and Therapy » Volume 7

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

Authors Braicu E, Luketina H, Richter R, Cacsire Castillo-Tong D, Lambrechts S, Mahner S, Concin N, Mentze M, Zeillinger R, Vergote I, Sehouli J

Received 2 April 2014

Accepted for publication 2 May 2014

Published 11 September 2014 Volume 2014:7 Pages 1563—1569


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5

Elena Ioana Braicu,1 Hrvoje Luketina,1 Rolf Richter,1 Dan Cacsire Castillo-Tong,2 Sandrina Lambrechts,4 Sven Mahner,5 Nicole Concin,6 Monika Mentze,1 Robert Zeillinger,2,3 Ignace Vergote,4 Jalid Sehouli1

1Department of Gynecology, European Competence Center for Ovarian Cancer, Charité – Universitätsmedizin Berlin, Berlin, Germany; 2Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 3Ludwig Boltzmann Cluster Translational Oncology, General Hospital of Vienna, Vienna, Austria; 4Department of Obstetrics and Gynecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Leuven, Belgium; 5Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 6Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria

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 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.

Keywords: HIF1α, surgical outcome, platinum response, survival, primary epithelial ovarian cancer, predictive factors

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]