Abstract 4500: Clinical significance of survivin expression in urothelial carcinoma of the bladder

Abstract

Abstract Objective: Survivin is one of the inhibitors of apoptosis protein family and plays an important role in carcinogenesis. Survivin also has been reported to be related with poor clinical outcome in various malignancies. The aim of this study is to examine the association between survivin expression and clinical outcome in urothelial carcinoma of the bladder. Materials and methods: A total of 56 histopathologically confirmed urothelial carcinoma of bladder (UCB) patients were recruited from the Department of Urology of Chiayi Christian Hospital and Chi-Mei Medical Center from August 2006 to May 2007. Immunohistochemistry (IHC) analysis was performed to determine the expression level of survivin in tumor and adjacent normal tissues. One normal human urothelial cell: HUC4449 and nine urothelial carcinoma cell lines which are TSGH8301, 5637, BFTC905, BFTC909, HT1376, TCC SUP, J82, T24 and HT1197 for survivin mRNA analysis by quantitative real-time PCR. The –31 C/G polymorphism in survivin gene was determined using PCR-RFLP method. The effects of a higher expression level of survivin on disease-free survival (DFS) and overall survival (OS) were estimated using Cox proportional hazard models. Results: The frequency of low, moderate and higher expression of survivin in tumor tissues of UCB were 16.1%, 39.3% and 44.6%, respectively. The frequency of high expression of survivin was significantly higher in muscle-invasive tumors (66.6%) than in non-muscle invasive tumors (34.2%) (P=0.042). The frequency of high expression of survivin was significantly higher in poor-differentiated (85.7%) than in moderate- differentiated tumors (30.8%) (P= 0.0014). The survivin mRNA expression (Log2 fold change were 3.41∼5.30) in various grade (G2-G4) urothelium carcinoma cell lines were all higher than normal human urothelial cell. Moreover, the higher frequency of risk genotypes (C/C+C/G) was observed in median and high survivn expression groups. In a multivariate analysis, high survivin expression was predictive of inferior OS (HR= 12.3, P=0.02). Conclusion: These findings suggest that the high expression of survivin is not only associated with tumor stage and grade of tumors but also may be predictive of inferior overall survival of urothelail carcinoma of the bladder. Keywords: survivin; bladder; urothelial carcinoma; immunohistochemistry, disease-free survival; overall survival Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4500. doi:1538-7445.AM2012-4500