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Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2β1 Is Associated with Aggressive Epithelial Ovarian Cancer

ORCID
0000-0001-6589-4736
Affiliation
Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Czogalla, Bastian;
Affiliation
Department of General, Visceral and Transplant Surgery, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Dötzer, Katharina;
Affiliation
Department of General, Visceral and Transplant Surgery, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Sigrüner, Nicole;
Affiliation
Gynecology and Obstetrics Clinic, Klinikum Dritter Orden, Menzinger Straße 44, 80638 Munich, Germany
von Koch, Franz Edler;
Affiliation
Department of Obstetrics and Gynecology, Klinikum Rechts der Isar, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany
Brambs, Christine E.;
Affiliation
Department of Obstetrics and Gynecology, Starnberg Hospital, Oßwaldstraße 1, 82319 Starnberg, Germany
Anthuber, Sabine;
ORCID
0000-0002-0173-8838
Affiliation
Department of Obstetrics and Gynecology, Munich Clinic Harlaching, Sanatoriumsplatz 2, 81545 Munich, Germany
Frangini, Sergio;
Affiliation
Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Burges, Alexander;
Affiliation
German Cancer Consortium (DKTK), Partner Site Munich, Pettenkoferstraße 8a, 80336 Munich, Germany
Werner, Jens;
Affiliation
Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
Mahner, Sven;
Affiliation
German Cancer Consortium (DKTK), Partner Site Munich, Pettenkoferstraße 8a, 80336 Munich, Germany
Mayer, Barbara

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.

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