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OBJECTIVE To investigate the association between the expression of uroplakin III (UPIII) and the prognosis of patients with urothelial carcinoma of the upper urinary tract, as uroplakins are urothelium-specific markers of terminal urothelial differentiation. PATIENTS AND METHODS Clinicopathological and follow-up data from 71 patients who had undergone radical nephroureterectomy and lymph node dissection or sampling for urothelial carcinoma of the upper urinary tract were reviewed. The expression of UPIII was evaluated immunohistochemically in surgical specimens. Cancer-specific survival was calculated using Kaplan–Meier plots. Prognostic values of clinicopathological variables including UPIII expression status, tumour stage and grade were evaluated by univariate analyses, followed by multivariate analysis using the Cox proportional-hazard model. RESULTS In all specimens there was intense UPIII immunoreactivity of umbrella cells of normal urothelium. In tumour samples, UPIII expression was positive in 75% of ≤ pT1 tumours and 40% of ≥ pT2 ( P = 0.02), and in 65% of grade 1–2 tumours and 33% of grade 3 ( P = 0.009). Of the 71 patients, 21 died from the disease during the median follow-up of 61 months. The cancer-specific survival of patients with negative UPIII expression was significantly worse than that of those with positive UPIII expression (5-year cancer-specific survival, 100% vs 46%, P < 0.001). Neither patient age at diagnosis, histological grade, sex, or multiplicity of the tumour had significant prognostic value. Multivariate analysis revealed that UPIII expression was the most powerful prognostic indicator ( P < 0.001) followed by tumour stage ( P = 0.04) and lymph node metastasis ( P = 0.05). CONCLUSION The present data suggest that UPIII expression is a powerful prognostic factor in patients with upper urinary tract urothelial carcinoma. [ABSTRACT FROM AUTHOR]