Nuclear factor (NF)-kappaB has been reported to be constitutively activated in various human neoplasms. However, its clinical significance in bladder urothelial carcinoma (UC) remains an unresolved issue. We conducted this study trying to elucidate the role of NFkappaB in bladder UC and its potential prognostic significance, by quantifying immunohistochemically the levels of p65/RelA expression in paraffin-embedded tissue from 116 patients. Some of the cases had previously been stained for cellular FLICE-like inhibitory protein (c-FLIP) and bcl-2. Seventy-four cases displayed concurrent cytoplasmic and nuclear immunoreactivity, whereas 18 only nuclear immunoexpression and 21 only cytoplasmic immunoexpression, and the remaining three cases were negative for p65/RelA. Nuclear p65/RelA expression was positively associated with tumour grade and T-category (p=0.0001 in both cases). In addition, cytoplasmic p65/RelA expression was lower in advanced T-category (p=0.0030). Moreover, p65/RelA nuclear expression was positively correlated with c-FLIP (p=0.0109) and bcl-2 (p=0.0452). p65/RelA nuclear expression adversely affected survival in both univariate and multivariate analysis in superficial (Ta-T1; p=0.0010 and p=0.0008) as well as in muscle-invasive carcinomas (T2-T4; p=0.0004 and p=0.0003). Our results demonstrate that NF-kappaB nuclear expression is correlated with histologic grade and T category in bladder UC. Moreover, NF-kappaB nuclear expression emerges as an independent prognosticator of adverse significance, conveying information beyond that obtained by standard clinicopathological prognosticators.

No abstract

No abstract

( 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. KEYWORDS RPA, immunoexpression, bladder urothelial carcinomaWhat'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