Jun Guan1,2, Silvia Darb-Esfahani2,3, Rolf Richter1,2, Eliane T Taube2,3, Ilary Ruscito1,2,4, Sven Mahner2,5,6, Linn Woelber2,5, Katharina Prieske2,5, Nicole Concin2,7, Ignace Vergote2,8, Els Van Nieuwenhuysen2,8, Patriciu Achimas-Cadariu2,9, Joanna Glajzer1,2, Hannah Woopen1,2, Mandy Stanske1, Hagen Kulbe1,2, Carsten Denkert1,2, Jalid Sehouli1,2, Elena Ioana Braicu10,11. 1. Department of Gynecology, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. 2. Tumorbank Ovarian Cancer Network, Berlin, Germany. 3. Berlin Institute of Health, Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. 4. Laboratory of Cell Therapy and Tumor Immunology, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. 5. Department of Gynecology, University-Medical-Center Hamburg-Eppendorf, Hamburg, Germany. 6. Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany. 7. Department of Gynecology, Medical University of Innsbruck, Innsbruck, Austria. 8. Department of Gynecology and Obstetrics, University Hospital Leuven, Leuven, Belgium. 9. Department of Surgical and Gynecological Oncology, The Oncology Institute Cluj-Napoca, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania. 10. Department of Gynecology, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. elena.braicu@charite.de. 11. Tumorbank Ovarian Cancer Network, Berlin, Germany. elena.braicu@charite.de.
Abstract
OBJECTIVE: The impact of angiogenesis on long-term survival of high-grade serous ovarian cancer (HGSOC) patients remains unclear. This study investigated whether angiogenic markers correlated with 5-year progression-free survival (PFS) in a large cohort of matched advanced HGSOC tissue samples. METHODS: Tumor samples from 124 primary HGSOC patients were retrospectively collected within the Tumor Bank Ovarian Cancer ( http://www.toc-network.de ). All patients were in advanced stages (FIGO stage III-IV). No patient had received anti-angiogenesis therapy. The cohort contains 62 long-term survivors and 62 controls matched by age and post-surgical tumor residuals. Long-term survivors were defined as patients with no relapse within 5 years after the end of first-line chemotherapy. Controls were patients who suffered from first relapse within 6-36 months after primary treatment. Samples were assessed for immunohistochemical expression of vascular endothelial growth factor (VEGF) A and VEGF receptor 2 (VEGFR2). Expression profiles of VEGFA and VEGFR2 were compared between the two groups. RESULTS: Significant correlation between VEGFA and VEGFR2 expression was observed (p < 0.0001, Spearman coefficient 0.347). A high expression of VEGFR2 (VEGFR2high) was found more frequently in long-term survivors (77.4%, 48/62) than in controls (51.6%, 30/62, p = 0.001), independent of FIGO stage and VEGFA expression in multivariate analysis (p = 0.005). Also, VEGFR2high was found the most frequently in women with PFS ≥ 10 years (p = 0.001) among all 124 patients. However, no significant association was detected between VEGFA expression and 5-year PFS (p = 0.075). CONCLUSIONS: VEGFR2 overexpression significantly correlated with long-term PFS in HGSOC patients, independent of age, FIGO stage, tumor residual and VEGFA expression.
OBJECTIVE: The impact of angiogenesis on long-term survival of high-grade serous ovarian cancer (HGSOC) patients remains unclear. This study investigated whether angiogenic markers correlated with 5-year progression-free survival (PFS) in a large cohort of matched advanced HGSOC tissue samples. METHODS:Tumor samples from 124 primary HGSOC patients were retrospectively collected within the Tumor Bank Ovarian Cancer ( http://www.toc-network.de ). All patients were in advanced stages (FIGO stage III-IV). No patient had received anti-angiogenesis therapy. The cohort contains 62 long-term survivors and 62 controls matched by age and post-surgical tumor residuals. Long-term survivors were defined as patients with no relapse within 5 years after the end of first-line chemotherapy. Controls were patients who suffered from first relapse within 6-36 months after primary treatment. Samples were assessed for immunohistochemical expression of vascular endothelial growth factor (VEGF) A and VEGF receptor 2 (VEGFR2). Expression profiles of VEGFA and VEGFR2 were compared between the two groups. RESULTS: Significant correlation between VEGFA and VEGFR2 expression was observed (p < 0.0001, Spearman coefficient 0.347). A high expression of VEGFR2 (VEGFR2high) was found more frequently in long-term survivors (77.4%, 48/62) than in controls (51.6%, 30/62, p = 0.001), independent of FIGO stage and VEGFA expression in multivariate analysis (p = 0.005). Also, VEGFR2high was found the most frequently in women with PFS ≥ 10 years (p = 0.001) among all 124 patients. However, no significant association was detected between VEGFA expression and 5-year PFS (p = 0.075). CONCLUSIONS:VEGFR2 overexpression significantly correlated with long-term PFS in HGSOC patients, independent of age, FIGO stage, tumor residual and VEGFA expression.