Immunohistochemical study of urothelial carcinoma of the urinary bladder: diagnostic and therapeutic implications

Abstract

Invasive urothelial carcinoma (UC) is the most common form of urinary bladder cancer and most dogs ultimately die of the disease. It is derived from urothelium, a unique, highly specialised epithelium which lines the lower urinary tract and functions as a physical barrier as well as a sensory structure. Canine UC is believed to be an appropriate animal model because canine UC shares many characteristics with human UC. A substantive comparative study on tumorigenic molecules expressed by canine and human UC is anticipated as an important development toward understanding the mechanism. Tyrosine kinases are proteins that phosphorylate other proteins on tyrosine residues. Evidence suggests that in both human and veterinary patients, tyrosine kinases are often abnormally activated in malignant tumours. Examples of receptor tyrosine kinases include Kit and VEGFR2, all of which are known to be dysregulated forms of cancer. Toceranib phosphate (Palladia®; Pfizer Animal Health, Madison, NJ, USA) is an oral oxindole receptor tyrosine kinase inhibitor that blocks the activity of VEGFR2, PDGFRα/β, FLT-3, KIT and CSFR1. The aims of this study were to extend the knowledge about the immunohistochemical factors involved in urothelial carcinogenesis and identify risk factors for development of UC.