T-cell immunoglobulin mucin-3 expression in bladder urothelial carcinoma: Clinicopathologic correlations and association with survival

Background T cell immunoglobulin mucin‐3 (Tim‐3) was initially recognized as a pivotal immune checkpoint inhibitor that maintains immune homeostasis and tolerance. Recently, Tim‐3 has been demonstrated to play an important role in tumor‐associated immune suppression and aberrant Tim‐3 expression has been reported in several human malignancies. However, the role of Tim‐3 in bladder urothelial carcinoma (BUC) remains largely unknown. The present study aims to investigate Tim‐3 expression in BUC and analyze correlations with clinicopathologic outcomes and postoperative survival. Methods Tim‐3 protein expressions were detected in paraffin embedded sections from 100 patients with BUC by immunohistochemistry. Expressions were correlated with clinicopathologic outcomes and postoperative survival. Results Tim‐3 protein was over‐expressed in bladder cancer cells, tumor infiltrating lymphocytes and endothelial cells from patients with BUC. The expression levels of Tim‐3 were significantly correlated with advanced pathological grade and T stage. Moreover, another immune checkpoint molecule programmed death receptor‐1(PD‐1) was also over‐ expressed in BUC tissues and had a significant correlation with Tim‐3. Multivariate analysis showed that Tim‐3 expression, as well as PD‐1 expression was both independent predictors of disease‐free survival and overall survival in patients with BUC. Conclusion Tim‐3 over‐expression implies adverse clinical outcomes for BUC, which suggests it is a potential prognostic biomarker and a novel therapeutic target in BUC. J. Surg. Oncol. 2015; 112:430–435. © 2015 Wiley Periodicals, Inc.