Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2β1 Is Associated with Aggressive Epithelial Ovarian Cancer
Bastian Czogalla,
Katharina Dötzer,
Nicole Sigrüner,
Franz Edler von Koch,
Christine E. Brambs,
Sabine Anthuber,
Sergio Frangini,
Alexander Burges,
Jens Werner,
Sven Mahner,
Barbara Mayer
Affiliations
Bastian Czogalla
Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Katharina Dötzer
Department of General, Visceral and Transplant Surgery, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Nicole Sigrüner
Department of General, Visceral and Transplant Surgery, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Franz Edler von Koch
Gynecology and Obstetrics Clinic, Klinikum Dritter Orden, Menzinger Straße 44, 80638 Munich, Germany
Christine E. Brambs
Department of Obstetrics and Gynecology, Klinikum Rechts der Isar, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany
Sabine Anthuber
Department of Obstetrics and Gynecology, Starnberg Hospital, Oßwaldstraße 1, 82319 Starnberg, Germany
Sergio Frangini
Department of Obstetrics and Gynecology, Munich Clinic Harlaching, Sanatoriumsplatz 2, 81545 Munich, Germany
Alexander Burges
Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Jens Werner
German Cancer Consortium (DKTK), Partner Site Munich, Pettenkoferstraße 8a, 80336 Munich, Germany
Sven Mahner
Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Barbara Mayer
German Cancer Consortium (DKTK), Partner Site Munich, Pettenkoferstraße 8a, 80336 Munich, Germany
Hepatocyte growth factor receptor (HGFR), also known as c-mesenchymal–epithelial transition factor (c-MET), plays a crucial role in the carcinogenesis of epithelial ovarian cancer (EOC). In contrast, the mechanisms contributing to aberrant expression of HGFR in EOC are not fully understood. In the present study, the expression of HGFR with its prognostic and predictive role was evaluated immunohistochemically in a cohort of 42 primary ovarian cancer patients. Furthermore, we analyzed the dual expression of HGFR and other druggable biomarkers. In the multivariate Cox regression analysis, high HGFR expression was identified as an independent prognostic factor for a shorter progression-free survival (PFS) (hazard ratio (HR) 2.99, 95% confidence interval (CI95%) 1.01–8.91, p = 0.049) and overall survival (OS) (HR 5.77, CI95% 1.56–21.34, p = 0.009). In addition, the combined expression of HGFR, human epidermal growth factor receptor 2 (Her2/neu), epithelial growth factor receptor (EGFR), insulin-like growth factor 1 (IGF1R), Mucin-1 and Integrin α2β1 further significantly impaired PFS, platinum-free interval (PFI) and OS. Protein co-expression analyses were confirmed by transcriptomic data in a large, independent cohort of patients. In conclusion, new biomarker-directed treatment targets were identified to fight poor prognosis of primary EOC.
