The clinical course of patients initially with noninvasive transitional cell carcinomas (TCCs) of the urinary bladder is often unpredictable on the basis of conventional morphologic criteria. Studies by the applicant and other investigators have indicated that tumor reactivity for the A,B,H and Lewis blood group antigens are useful in predicting the subsequent course; reduction of antigenic reactivity is associated with a higher likelihood of recurrence and/or invasion. The proposed studies will extend and clarify these initial observations. Specifically, we intend to develop methodology for the ultrastructural demonstration of blood group related antigens (BG Ags) in normal and neoplastic urothelium. This will enable us to discriminate between cell surface and intracellular antigenic reactivity and, also, to identify the organelles involved in the biosynthesis of BG Ags and their relation to defective antigen expression in neoplastic cells. A second objective of the proposed studies is to combine immunohistological observations with qualitative and quantitative analysis of tissue glycolipids utilizing radio-immune thin layer chromatography. This analysis will faciltate quantitative comparisons of BG Ag levels in urothelial neoplasms and, also, allow the demonstration of possible qualitative differences in the structure of tumor BG substances. Finally, we intend to examine the mechanism(s) responsible for the previously observed variability in antigen detectability depending on whether lectins, polyclonal, or monoclonal antibodies are used. The results of each of the above methodologies will be correlated with conventional morphology and clinical outcome. It is hoped that the proposed studies will lead to new insights into the mechanisms of altered BG Ag reactivity in TCCs and, thereby, improve our understanding of the biological behavior of these tumors and the management of patients harboring them.
