Stromal expression of VEGF-A and VEGFR-2 in prostate tissue is associated with biochemical and clinical recurrence after radical prostatectomy.

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. Prostate. © 2015 Wiley Periodicals, Inc.

Prostate. 2015 Aug 13. doi: 10.1002/pros.23048. [Epub ahead of print]

Nordby Y1,2, Andersen S1,3, Richardsen E4,5, Ness N5, Al-Saad S4,5, Melbø-Jørgensen C5, Patel HR1,2, Dønnem T1,3, Busund LT4,5, Bremnes RM1,3.

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.

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