Background/aims: Prostate cancer is aheterogeneous disease, ranging from indolent and slow growing to aggressive andlethal.
Due to insufficient prognostic tools, there is a significant overtreatmentof patients with harmless disease. Differentiating which patients benefit fromradical treatments remains a huge challenge, and there is an urgent need tofind new and better prognostic tools that may aid in treatment allocation. Angiogenesisis a well-studied hallmark of cancer. Without sufficient blood flow, themalignant tumor cannot grow to a self-sustaining tumor of significant size. Theprognostic impacts of selected angiogenic biomarkers in our cohort wereexplored, with the aim to uncover novel biomarkers to contribute to theknowledge of prostate cancer aggressiveness for improved risk stratification.In addition, a deeper understanding of the molecular characteristics andfunctional pathways for different stages in prostate cancer is essential in orderto succeed in development of novel therapeutic agents for targeted therapy. Methods: Patient data and prostatectomyspecimens from 535 Norwegian patients treated for prostate cancer with curativeintent were collected.
Using tissue microarrays with several cores frompredefined areas of the specimens, staining with immunohistochemistry and in-situ hybridization were performed forrenowned angiogenic biomarkers. Correlations between expression levels ofbiomarkers and patients endpoints were calculated.Main results: High expression of vascularendothelial growth factor receptor 2 (VEGFR-2) in either stroma or epitheliumwas independently associated with a higher incidence of prostate cancer relapse(HR = 4.
56, p = 0.038). A high combined expression of either VEGFR-2, vascularendothelial growth factor A (VEGF-A) or both in stroma was independently associatedwith a higher incidence of biochemical failure (HR = 1.77, p = 0.011). Highstromal expression of platelet derived growth factor receptor ? (PDGFR-?) wasindependently associated with clinical relapse (HR = 2.17, p = 0.
010) andbiochemical failure (HR = 1.58, p = 0.002).
High expression of microRNA (miR)-205in normal epithelium was independently associated with biochemical relapse (HR= 1.64, p = 0.003).
When assessing expression of miR-205, we found novelindications of a crosstalk between normal epithelium and tumor epithelium,suggesting an anti-cancerogenous function of normal epithelium.