Evaluation of RNA-binding motif protein 3 expression in urothelial carcinoma of the bladder: an immunohistochemical study

BACKGROUND: RNA-binding motif protein 3 (RBM3), involved in cell survival, has paradoxically been linked to both oncogenesis as well as an increased survival in several cancers, including urothelial carcinoma (UCA). METHODS: The putative prognostic role of RBM3 was studied using cystectomy specimens with 152 invasive UCA with 35 matched metastases, 65 carcinomas in situ (CIS), 22 high-grade papillary UCAs (PAP), and 112 benign urothelium cases. RESULTS: The H-score (HS, staining intensity × % of positive cells) was used for RBM3 immunoexpression. CIS showed the highest HS (mean = 140) followed by benign urothelium (mean = 97). Metastases showed higher HS than primary invasive UCA (P ≤ 0.0001), and high HS was associated with a lower pT stage (P ≤ 0.0001) and a trend toward the absence of lymphovascular invasion (LVI, P = 0.09), but not pN stage (P = 0.35) and surgical margin status (P = 0.81). Univariate analysis (UVA) of disease recurrence only showed an association between pN stage and LVI (P = 0.005 and 0.03, respectively). On UVA of mortality, pT stage was strongly associated with death (P = 0.01) while pN stage, LVI, surgical margin status, and HS were not. Multivariate analysis confirmed the lack of HS association with recurrence (P = 0.08) and death (P = 0.32). CONCLUSIONS: Stronger RBM3 immunoexpression correlated with lower stage tumors and a diminished risk for LVI. However, RBM3 does not seem to carry a prognostic significance for clinical outcome (recurrence and mortality). The exact prognostic role of RBM3 in UCA is yet to be determined.