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

• Published in: BJU international Vol. 108; no. 2b; pp. E59 - E65
• Main Authors: Levidou, Georgia, Gakiopoulou, Hariklia, Kavantzas, Nikolaos, Saetta, Angelica A., Karlou, Maria, Pavlopoulos, Petros, Thymara, Irene, Diamantopoulou, Kalliopi, Patsouris, Efstratios, Korkolopoulou, Penelope
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2011
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - metabolism; bladder urothelial carcinoma; Cyclin D1 - metabolism; Female; Humans; immunoexpression; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Replication Protein A - metabolism; RPA; Survival Analysis; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Urothelium - chemistry
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2010.09828.x

What’s known on the subject? and What does the study add? The prognostic utility of cyclin D1 in non‐muscle and muscle‐invasive urothelial bladder carcinomas has already been examined by our group and our investigators previously. Moreover, recent investigations have shown that RPA protein expression may be implicated in the pathogenesis of various malignant tumours. In this study, RPA1 and RPA2 overexpression seems to be more important during early T‐categories of bladder carcinogenesis, showing similar kinetics with cyclin D1, whereas 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. 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 ρ= 0.309, P < 0.001). Both RPA1 and RPA2 LIs were positively correlated with cyclin D1 expression (ρ= 0.354, P < 0.001 and ρ= 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.