Uroplakins (UPs) are a family of transmembrane proteins (UPs Ia, Ib, II and III) that are specific differentiation products of urothelial cells. In non-neoplastic mammalian urothelium, UPs are expressed in the luminal surface plasmalemma of superficial (umbrella) cells, forming complexes of 16nm crystalline particles. Anti-UPIII was detectable immunohistochemically in 29 of 55 primary (53%) and 23 of 35 metastatic (66%) urothelial carcinomas, whereas many non-urothelial carcinomas were anti-UPIII negative. The authors concluded that anti-UPIII should be a valuable marker, especially for the specific identification of urothelial carcinomas in patients with metastases of unknown primary site. Olsburgh et al. studied anti-UPIII gene expression in normal urothelium and bladder cancer specimens, and found that expression was absent after malignant transformation. Thus, UP expression might reflect the malignant potential of urothelial cancer cells as well as being cytodifferential markers of urothelial cells. Ohtsuka et al. concluded in their studies that anti-UPIII expression was strongly associated with lower tumor grades, that lack of UPIII expression in urothelial tumors of the upper urinary tract was associated with much higher rates of metastases, and that 5-year specific survival was much worse for anti- UPIII negative tumors (54%) than for anti-UPIII positive tumors (100%). Apparently, UPIII expression characteristics are a better indicator of the malignant potential of urothelial carcinomas than the grade of these tumors.