Ubiquilin2 as a novel marker for detection of urothelial carcinoma cells in urine.

Abstract

Ubiquilin 2 (UBQLN2), an ubiquitin-related protein, is strongly expressed in urothelial carcinoma cells, in contrast to no or less expression in non-neoplastic cells; it protects cancer cells from reactive oxygen species (ROS)-induced cytotoxicity. In this study, we investigated whether UBQLN2 immunostaining, using liquid-based cytology sample could improve the accuracy of cytological urine diagnosis. Two-hundred and forty-five urinary samples, including 143 negative controls and 102 urothelial carcinomas, consisting of 42 low-grade and 60 high-grade urothelial carcinomas, were used for immunocytochemical analysis of UBQLN2. Urothelial carcinoma cells were positive for UBQLN2-staining, while non-neoplastic cells, including renal tubular cells and degenerative atypical cells, were negative. Interestingly, percentage of nuclear stain immunopositive for UBQLN2 was significantly higher in carcinoma cells with high grade/invasive phenotype than in those with low grade/noninvasive phenotype. UBQLN2 immunostaining had an overall sensitivity of 87.6%, specificity of 98.6%, positive predictive value of 97.8% and negative predictive value of 92.8% for the detection of urothelial carcinoma. UBQLN2 immunostaining is a practical test for urine cytology, even in samples with few cells, with slight atypia or severe degenerative changes. In addition, it allows prediction of tumor grade and stage by examining the cellular localization of UBQLN2.