Neoglycoprotein binding to normal urothelium and grade-dependent changes in bladder lesions.

Chemical conjugation of carbohydrate derivatives to a labelled carrier protein makes it possible to monitor the presence of specific sugar-dependent binding to routinely processed tissue sections. Different levels of cytoplasmic staining were observed in normal urothelium for the applied probes that expose a beta-D-galactoside, alpha- or beta-N-acetyl-D-galactosaminide, beta-N-acetyl-D-glucosaminide, alpha-D-mannoside, alpha-L-fucoside or a-D-glucoside, respectively. These moieties are crucial parts of the recognition sites in cellular glycoconjugates for plant lectins. The extent of staining invariably increased from the basal to the luminal cell layer. No nuclear staining was observed. Within the 18 cases of bladder lesions studied, the appearance of nuclear staining was characteristic of transitional cell carcinoma, its correlation to the histologic grade being dependent on the type of neoglycoprotein. Cytoplasmic staining revealed at least two patterns of grade-dependent variations, namely rather constant expression for lactose-mannose-, fucose- and maltose-specific sites and an initial increased followed by a loss of binding activity at the highest level of cellular atypia for the other three types of probe. Intratumoral heterogeneity was especially visible in tumors of this group. Interestingly, the known positive correlation of presence of the Thomsen-Frieden rich antigen with the level of cellular atypia, monitored with peanut agglutinin, could be extended to the expression of respective receptor sites, which was experimentally feasible due to the synthesis of this disaccharide structure and its immobilization to the carrier protein.