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.


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.
National and Kapodistrian University of Athens, Laiko Hospital, First Department of Pathology, Athens, Greece. glevidou@yahoo.gr
Georgia
G
Levidou
Hariklia
H
Gakiopoulou
Nikolaos
N
Kavantzas
Angelica A
AA
Saetta
Maria
M
Karlou
Petros
P
Pavlopoulos
Irene
I
Thymara
Kalliopi
K
Diamantopoulou
Efstratios
E
Patsouris
Penelope
P
Korkolopoulou
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D051716:Replication Protein A / Q000378:metabolism*; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000737:chemistry
D014408:Biomarkers, Tumor; C497167:RPA1 protein, human; D051716:Replication Protein A; D019938:Cyclin D1; C516794:RPA2 protein, human