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