Context.-Uroplakin II is a 15-kDa protein component of the urothelial plaques that enhance the permeability barrier and strength of the urothelium. Studies have shown uroplakin II messenger RNA to be expressed in bladder cancer tissues and peripheral blood of patients with urothelial carcinoma. Little is known about the protein expression of uroplakin II in urothelial carcinoma, possibly because of the absence of a commercially available uroplakin II antibody. Pathologists have used the uroplakin III antibody (AU1) to identify tumors of urothelial origin; however, the use of AU1 is limited because of its poor sensitivity.Objectives.-To evaluate a newly developed mouse monoclonal uroplakin II antibody (BC21) in urothelial carcinoma and to compare it with previously developed mouse monoclonal uroplakin III (BC17 and AU1).Design.-Uroplakin II and III antibodies were optimized for staining using a horseradish peroxidase-polymer detection system and were visualized with 3,3 0 -diaminobenzidine.Results.-BC21, BC17, and AU1 demonstrated sensitivities in urothelial carcinoma of the bladder of 79% (44 of 56), 55% (31 of 56) (P ¼ .002), and 34% (19 of 56) (P , .001), respectively. Subsequently, the increased staining sensitivity and intensity of BC21, compared with BC17, was validated in a larger study (134 of 174; 77% and 94 of 174; 54%, respectively) (P , .001). BC21 was found to be highly specific when evaluated in various normal and neoplastic tissues, including prostatic and renal carcinomas.Conclusions. 1 This cancer is particularly associated with high recurrence and progression rates. About 70% of patients with superficial bladder cancer will experience tumor recurrence, and 10% to 15% of that subpopulation will eventually progress to muscle invasion.
2Early diagnosis, when the disease is still at a localized stage, increases the chance of successful treatment. The survival rate for in situ urinary bladder cancer is 97%. Tissue-based biomarkers for early diagnosis of bladder cancer are a major clinical need. Urothelial carcinoma (UC) originates in the urothelium and accounts for more than 90% to 95% of all bladder tumors. Adenocarcinoma and squamous cell carcinoma make up about 1% and 5%, respectively, of bladder carcinomas. Biomarkers expressed in the urothelium, such as uroplakins, could be valuable markers of UC of the bladder. Pathologists have used uroplakin (UP) III (clone AU1) to establish the urothelial origin of the tumor; however, the use of AU1 has been limited because of its poor sensitivity.The asymmetric-unit membrane plaques of the urothelium maintain the blood-urine barrier and prevent cells from rupturing during bladder distention. The molecular constituents of those plaques comprise four transmembrane UP isoforms: UPIa, UPIb, UPII, and UPIII, which are specific differentiation products of the urothelial cells. The UPII is a 15-kDa protein component of the urothelial plaques that enhance the permeability barrier and strength of the urothelium. 4 The expression of UPII is aberrant in urothelial car...