Prognostic significance of replication protein A (RPA) expression levels in bladder urothelial carcinoma

OBJECTIVE To elucidate the role of replication protein A (RPA) in both superficial (Ta-T1) and muscle-invasive (T2-T4) urothelial carcinomas (UCs), investigating its potential prognostic usefulness. PATIENTS AND METHODS Paraffin-embedded tissue from 156 patients with bladder UC was immunostained for RPA1 and RPA2. RESULTS RPA1 and RPA2 labelling indexes (LIs) decreased with increasing histological grade (both P < 0.001) and T-category in the entire cohort (P = 0.008 and P < 0.001, respectively) and in muscle-invasive carcinomas (P = 0.014 and P = 0.012, respectively). RPA1 expression was positively correlated with RPA2 (Spearman's correlation coefficient. = 0.309, P < 0.001). Both RPA1 and RPA2 LIs were positively correlated with cyclin D1 expression (rho = 0.354, P < 0.001 and rho = 0.934, P < 0.001). In survival analysis of the entire cohort decreased RPA2 and RPA1 correlated with a lesser probability of survival (P < 0.001 and P = 0.018). In non-muscle-invasive tumours (Ta-T1) only lower RPA2 (P < 0.001) was correlated with shortened survival, whereas in muscle-invasive tumours (T2-T4) decreased RPA2 and RPA1 expression levels were associated with adverse prognosis (P = 0.035 and P = 0.042, respectively). In multivariate survival analysis of the entire cohort and in non-muscle-invasive cases RPA2 expression remained significant, even when adjustment for cyclin D1 expression was applied. CONCLUSIONS RPA1 and RPA2 overexpression seems to be more important during early T-categories of bladder carcinogenesis. Showing similar kinetics with cyclin D1. RPA2 expression emerges as a valuable marker of favourable prognosis in the entire cohort and in non-muscle-invasive tumours, supplementing the information obtained by standard clinicopathological prognosticators.