Lectinohistochemistry of human bladder cancer: loss of lectin binding structures in invasive carcinomas

With the purpose of studying changes in the expression of glycoconjugate structures in urothelium, nine different lectins (PNA, WGA, VFA, GSA II, STA, UEA I, LCA, DBA and HPA) with specificity for mono- or oligo-saccharides were used on formalin-fixed, paraffin-embedded tissue sections from 47 patients who had undergone surgical resection for bladder tumors and on normal urothelial biopsies from 10 patients. The tumors were graded and a lectinohistochemical method using biotinylated lectins and avidin-biotin-peroxidase complex was used to demonstrate the lectin binding. Positive staining reactions of cells in cytoplasm and on membranes were evaluated in the basal, the intermediate, and the luminal cell layers, respectively. In both normal and atypical urothelium lectin binding predominated in the luminal cell layer and decreased towards the basal cell layer. In normal urothelium all lectins stained greater than 66% of the cells in the luminal cell layer in cytoplasm and between 5 and 100% of the cells on membranes depending on the lectin used. A gradual loss of lectin-binding structures was seen with increasing grade of atypia. The range of this decrease varied considerably from one lectin to another, but it was consistently found that the percentage of cells stained in cytoplasm and on membranes decreased. A significantly lower percentage of cells stained in cytoplasm was found in invasive tumor cell-islands compared to normal urothelium. In invasive tumor cell-islands staining of cells on membranes was completely absent, except for HPA lectin that stained less than 10% of the cells. In conclusion, we demonstrate a dramatic decrease in lectin-binding carbohydrate structures associated with urothelial malignant progression.