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 16 nm crystalline particles. Moll et al. reported that UPIII was detectable immunohistochemically in 29 of 55 primary (53%) and 23 of 35 metastatic (66%) urothelial carcinomas, whereas many non- urothelial carcinomas were 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. Subsequently, Olsburgh et al. studied UP gene expression in normal urothelium and bladder cancer specimens, and found that expression was absent after malignant transformation. Ohtsuka et al. concluded in their studies that 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 five-year specific survival was much worse for UPIII negative tumors (54%) than for UPIII positive tumors (100%). Apparently UPIII expression is a better indicator of the malignant potential of the tumor than the grade of the tumor.
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