Objective: RNF2 is frequently overexpressed in several types of human cancer, but the status of RNF2 amplification and expression in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance is unclear.
Methods: In this study, the methods of immunohistochemistry and fluorescence in situ hybridization (FISH) were utilized to examine the protein expression and amplification of RNF2 in 184 patients of with UCBs who underwent radical cystectomy.
Results: Overexpression of RNF2 was found in 44.0% of UCBs. A highly significant association between overexpression of RNF2 with shortened patient overall and cancer specific survival (P<0.001, logrank test) was demonstrated. In different subsets of UCB patients, overexpression of RNF2 was also a prognostic indicator in patients with pT1, pT2, pN(-) and/or negative surgical margins (P<0.05). Importantly, RNF2 expression together with pT status and surgical margins status provided significant independent prognostic parameters in multivariate analysis (P<0.05). Additionally, a significant correlation (P=0.003) of overexpression of RNF2 with an increased UCB labeling index of Ki-67 was observed in this UCB cohort. FISH results showed that the amplification of RNF2 was examined in 8/79 (10.1%) of informative UCB cases; in each of the 7 cases with RNF2 amplification, overexpression of RNF2 was observed. In the remaining 71 informative cancers without RNF2 amplification, 25 (35.2%) cases showed overexpression of RNF2.
Conclusions: our findings suggested that overexpression of RNF2, as examined by immunohistochemistry, might serve as a novel prognostic biomarker and potential therapeutic target for UCB patients treated with radical cystectomy.
