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.


METHODS
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.
Department Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Department Urology, University Hospital of North Norway, Tromso, Norway.
Yngve
Y
Nordby
Department Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Department Oncology, University Hospital of North Norway, Tromso, Norway.
Sigve
S
Andersen
Department Clinical Pathology, University Hospital of North Norway, Tromso, Norway.|Department Medical Biology, The Arctic University of Norway, Tromso, Norway.
Elin
E
Richardsen
Department Medical Biology, The Arctic University of Norway, Tromso, Norway.
Nora
N
Ness
Department Clinical Pathology, University Hospital of North Norway, Tromso, Norway.|Department Medical Biology, The Arctic University of Norway, Tromso, Norway.
Samer
S
Al-Saad
Department Medical Biology, The Arctic University of Norway, Tromso, Norway.
Christian
C
Melbø-Jørgensen
Department Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Department Urology, University Hospital of North Norway, Tromso, Norway.
Hiten R H
HR
Patel
Department Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Department Oncology, University Hospital of North Norway, Tromso, Norway.
Tom
T
Dønnem
Department Clinical Pathology, University Hospital of North Norway, Tromso, Norway.|Department Medical Biology, The Arctic University of Norway, Tromso, Norway.
Lill-Tove
LT
Busund
Department Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Department Oncology, University Hospital of North Norway, Tromso, Norway.
Roy M
RM
Bremnes
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C581309:FLT4 protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3
angiogenesis; immunohistochemistry; prostate cancer; tissue microarray; veg