B215: Characterising expression of the pro-angiogenic regulator serine-arginine protein kinase 1 (SRPK1) in prostate cancer
1School of Physiology and Pharmacology, University of Bristol, Bristol, UK,2Department of Urology, Southmead Hospital, Bristol, UK,3School of Social and Community Medicine, University of Bristol, Bristol, UK,4Department of Cellular Pathology, Southmead Hospital, Bristol, UK
Vascular endothelial growth factor (VEGF) is one of the principal inducers of angiogenesis. VEGF pre-mRNA undergoes alternative splicing to produce both pro- and anti-angiogenic isoforms, the former of which are upregulated in prostate cancer (PCa). Preferential splicing of pro-angiogenic VEGF in PCa is regulated by serine-arginine protein kinase 1 (SRPK1). In this study we sought to investigate SRPK1 expression in PCa, its association with clinico-pathologic parameters, and its potential value as a biomarker for prediction of biochemical recurrence after radical prostatectomy.
Cores of tumour and benign tissue were extracted from radical prostatectomy specimens of 110 patients that underwent surgery at our centre during 2010/11. SRPK1 expression was evaluated using immunohistochemistry, with staining intensity scored from negative (0; no staining) to strong (3; clearly visible at low magnification) by two independent assessors that were blinded to clinical/pathological data.
Pathological staging ranged from pT2a-pT3b, with the majority of tumours being pT2c (n=51; 46%). Gleason grade ranged from 3+3=6 to 4+5=9, with the greatest proportion of cases being 3+4=7 (n=61; 55%). Expression of SRPK1 was higher in tumour compared with benign tissue, with a median difference in expression score of 2 (IQR 1-3; P<0.00001). SRPK1 expression correlated with higher pT stage (P=0.004), extracapsular extension (P=0.003) and extracapsular perineural invasion (P=0.008), but not with Gleason grade (P=0.21). Multivariate logistic regression demonstrated that SRPK1 expression was not associated with increased risk of biochemical recurrence following radical prostatectomy in this patient cohort (OR 0.92, CI 0.30-2.80).
SRPK1 expression is increased in human PCa compared to benign prostate tissue and is correlated with higher pT stage, extracapsular extension and extracapsular perineural invasion, suggesting it may facilitate development of a tumour microenvironment that favours growth and invasion. Further studies are required to evaluate SRPK1 as a potential therapeutic target in PCa.