['Tissue-specific expression is of key importance in gene therapy and can be achieved by using tissue-specific promoters to drive therapeutic gene expression. The uroplakin (UP) promoter is a powerful tool for bladder cancer gene therapy, but the role of UP protein in the bladder remains unknown. This study aimed to detect UP III expression in transitional cell carcinoma (TCC) of the bladder and to determine whether the role of UP III heterogeneity is associated with predicting disease recurrence and patient survival.', 'Immunohistochemical staining for UP III was carried out in 92 archival radical cystectomy and 38 normal specimens and correlated with pathologic features and clinical outcomes.', 'UP III expression was significantly decreased in bladder cancer tissues compared with normal controls (P <0.0001). Loss of UP III expression was associated with high-grade, muscle-invasive cancer, lymphovascular invasion (P <0.01), and decreased cancer-specific survival at a median follow-up of 25.3 months (P = 0.04). When adjusted for the effects of standard pathologic features, only lymph node metastases were associated with bladder cancer progression (P = 0.01) and mortality (P = 0.04).'] Is loss expression of uroplakin III associated with clinicopathologic features of aggressive bladder cancer?