Bovine Papillomavirus Type-2 (BPV-2) Infection and Expression of Uroplakin IIIb, a Novel Urothelial Cell Marker, in Urinary Bladder Tumors of Cows

Several immunohistochemical markers have been used to define the differentiation pattern of urothelial cell tumors of the urinary bladder. We investigated the expression of the recently characterized uroplakin (UP) IIIb, an urothelium-specific and differentiation-dependent protein, in 39 urothelial tumors of the urinary bladder in cows that had suffered from chronic enzootic hematuria for several years. Bovine papillomavirus type 2 DNA was amplified and UP IIIb protein was detected in all these tumors. In papillomas and papillary carcinomas, UP IIIb expression was mostly seen as superficial staining; luminal and peripheral patterns were also observed. In nonpapillary carcinomas, UP IIIb appeared to define clearly the cell membrane lining intercellular and intracellular lumina as well as the cell borders in deeper cell layers. In benign and malignant lesions, an intracytoplasmic immunoreactivity was also detected. Coarse intracytoplasmic UP IIIb-positive material close to the nucleus occurred in some malignant cells. Focally strong membraneous immunostaining that marked single cells with complete ringlike peripheral pattern was seen. Although UP IIIb expression does not seem to correlate with the biological behavior of urothelial tumors, it appears to be a highly sensitive marker for bovine urothelial tumors.