Periprostatic fat adipokine expression is correlated with prostate cancer aggressiveness in men undergoing radical prostatectomy for clinically localized disease.

Abstract

To investigate the relationship between periprostatic adipose tissue (PPAT) adipokine expression and prostate cancer (PCa) aggressiveness using both pathological features of radical prostatectomy (RP) and multiparametric magnetic resonance imaging ( MRI) variables. Sixty-nine men were recruited to assess immunohistochemical expression of tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) of periprostatic fat of RP specimens. Per cent immunopositivity was quantified on scanned slides using the Aperio Positive Pixel Count algorithm for PPAT TNFα, VEGF and androgen receptors. Periprostatic fat volume (PFV) was segmented on contiguous T1 -weighted axial MRI slices from the level of the prostate base to apex. PFV was normalized to prostate volume (PV) to account for variations in PV (normalized PFV = PFV/PV). MRI quantitative values (Kep , Ktrans and apparent diffusion coefficient) were measured from the PCa primary lesion using Olea Sphere software. Patients were stratified into three groups according to RP Gleason score (GS): ≤6, 7(3 + 4) and ≥7(4 + 3). The mean rank of VEGF and TNFα was significantly different between the groups [H(2) = 11.038, P = 0.004] and [H(2) = 13.086, P = 0.001], respectively. Patients with stage pT3 had higher TNFα (18.2 ± 8.95) positivity than patients with stage pT2 (13.27 ± 10.66; t [67] = -2.03, P = 0.047). TNFα expression significantly correlated with Ktrans (ρ = 0.327, P = 0.023). TNFα (P = 0.043), and VEGF (P = 0.02) correlated with high grade PCa (GS ≥ 7) in RP specimens and also correlated significantly with upgrading of GS from biopsy to RP histology. The expression levels of TNFα and VEGF on immunostaining significantly correlated with aggressivity of PCa. As biomarkers, these indicate the risk of having high grade PCa in men undergoing RP.