Background/aims: Prostate cancer is a
heterogeneous disease, ranging from indolent and slow growing to aggressive and
lethal. Due to insufficient prognostic tools, there is a significant overtreatment
of patients with harmless disease. Differentiating which patients benefit from
radical treatments remains a huge challenge, and there is an urgent need to
find new and better prognostic tools that may aid in treatment allocation. Angiogenesis
is a well-studied hallmark of cancer. Without sufficient blood flow, the
malignant tumor cannot grow to a self-sustaining tumor of significant size. The
prognostic impacts of selected angiogenic biomarkers in our cohort were
explored, with the aim to uncover novel biomarkers to contribute to the
knowledge of prostate cancer aggressiveness for improved risk stratification.
In addition, a deeper understanding of the molecular characteristics and
functional pathways for different stages in prostate cancer is essential in order
to succeed in development of novel therapeutic agents for targeted therapy.
Methods: Patient data and prostatectomy
specimens from 535 Norwegian patients treated for prostate cancer with curative
intent were collected. Using tissue microarrays with several cores from
predefined areas of the specimens, staining with immunohistochemistry and in-situ hybridization were performed for
renowned angiogenic biomarkers. Correlations between expression levels of
biomarkers and patients endpoints were calculated.
Main results: High expression of vascular
endothelial growth factor receptor 2 (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 VEGFR-2, vascular
endothelial growth factor A (VEGF-A) or both in stroma was independently associated
with a higher incidence of biochemical failure (HR = 1.77, p = 0.011). High
stromal expression of platelet derived growth factor receptor ? (PDGFR-?) was
independently associated with clinical relapse (HR = 2.17, p = 0.010) and
biochemical failure (HR = 1.58, p = 0.002). High expression of microRNA (miR)-205
in normal epithelium was independently associated with biochemical relapse (HR
= 1.64, p = 0.003). When assessing expression of miR-205, we found novel
indications of a crosstalk between normal epithelium and tumor epithelium,
suggesting an anti-cancerogenous function of normal epithelium.