Yngve Nordby1,2, Sigve Andersen1,3, Elin Richardsen4,5, Nora Ness5, Samer Al-Saad4,5, Christian Melbø-Jørgensen5, Hiten R H Patel1,2, Tom Dønnem1,3, Lill-Tove Busund4,5, Roy M Bremnes1,3. 1. Department Clinical Medicine, The Arctic University of Norway, Tromso, Norway. 2. Department Urology, University Hospital of North Norway, Tromso, Norway. 3. Department Oncology, University Hospital of North Norway, Tromso, Norway. 4. Department Clinical Pathology, University Hospital of North Norway, Tromso, Norway. 5. Department Medical Biology, The Arctic University of Norway, Tromso, Norway.
Abstract
BACKGROUND: There is probably significant overtreatment of patients with prostate cancer due to a lack of sufficient diagnostic tools to predict aggressive disease. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are potent mediators of angiogenesis and tumor proliferation, but have been examined to a limited extent in large prostate cancer studies. Meanwhile, recent promising results on VEGFR-2 inhibition have highlighted their importance, leading to the need for further investigations regarding their expression and prognostic impact. DESIGN: Using tissue microarray and immunohistochemistry, the expression of VEGFs (VEGF-A and VEGF-C) and their receptors (VEGFR-2 and VEGFR-3) were measured in neoplastic tissue and corresponding stroma from radical prostatectomy specimens in 535 Norwegian patients. Their expression was evaluated semiquantatively and associations with event-free survival were calculated. RESULTS: High expression of VEGFR-2 in either stroma or epithelium was independently associated with a higher incidence of prostate cancer relapse (HR = 4.56, P = 0.038). A high combined expression of either VEGF-A, VEGFR-2 or both in stroma was independently associated with a higher incidence of biochemical failure (HR = 1.77, P = 0.011). CONCLUSIONS: This large study highlights the prognostic importance of VEGF-A and VEGFR-2 stromal expression. Analyses of these biomarkers may help distinguish which patients will benefit from radical treatment. Together with previous studies showing efficiency of targeting VEGFR-2 in prostate cancer, this study highlights its potential as a target for therapy, and may aid in future selection of prostate cancer patients for novel anti-angiogenic treatment.
BACKGROUND: There is probably significant overtreatment of patients with prostate cancer due to a lack of sufficient diagnostic tools to predict aggressive disease. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are potent mediators of angiogenesis and tumor proliferation, but have been examined to a limited extent in large prostate cancer studies. Meanwhile, recent promising results on VEGFR-2 inhibition have highlighted their importance, leading to the need for further investigations regarding their expression and prognostic impact. DESIGN: Using tissue microarray and immunohistochemistry, the expression of VEGFs (VEGF-A and VEGF-C) and their receptors (VEGFR-2 and VEGFR-3) were measured in neoplastic tissue and corresponding stroma from radical prostatectomy specimens in 535 Norwegian patients. Their expression was evaluated semiquantatively and associations with event-free survival were calculated. RESULTS: High expression of VEGFR-2 in either stroma or epithelium was independently associated with a higher incidence of prostate cancer relapse (HR = 4.56, P = 0.038). A high combined expression of either VEGF-A, VEGFR-2 or both in stroma was independently associated with a higher incidence of biochemical failure (HR = 1.77, P = 0.011). CONCLUSIONS: This large study highlights the prognostic importance of VEGF-A and VEGFR-2 stromal expression. Analyses of these biomarkers may help distinguish which patients will benefit from radical treatment. Together with previous studies showing efficiency of targeting VEGFR-2 in prostate cancer, this study highlights its potential as a target for therapy, and may aid in future selection of prostate cancerpatients for novel anti-angiogenic treatment.
Authors: Annie Rochette; Nadia Boufaied; Eleonora Scarlata; Lucie Hamel; Fadi Brimo; Hayley C Whitaker; Antonio Ramos-Montoya; David E Neal; Alice Dragomir; Armen Aprikian; Simone Chevalier; Axel A Thomson Journal: Br J Cancer Date: 2017-02-02 Impact factor: 7.640
Authors: Josué Rivera-Pérez; María Del Rocío Monter-Vera; Cornelio Barrientos-Alvarado; Julia D Toscano-Garibay; Teresa Cuesta-Mejías; Javier Flores-Estrada Journal: Oncol Lett Date: 2017-11-08 Impact factor: 2.967