Altered reactivity for A, B, H antigens in transitional cell carcinomas of the urinary bladder. A study of the mechanisms involved.

Transitional cell carcinomas (TCCs) of the urinary bladder show variable blood group (BG) antigen reactivity even in the non-invasive stage. A correlation exists between the tumor reactivity and subsequent clinical course: when the expected BG antigen(s) is retained, the clinical course is favorable; absence of the expected antigen(s) denotes an aggressive potential. In the present study we investigated some of the possible mechanisms of altered BG antigen reactivity in TCCs. It was found that the "loss" of A, B, H reactivity is a quantitative phenomenon and the threshold for positive reactions depends on the method of tissue processing and the titer of the antisera. Thus, in the 35 cases studied, paraffin processing resulted in reduced reactivity compared to fresh-frozen tissue sections. The reactivity of tumors that appeared positive when tested with undiluted antisera was found reduced when quantitatively compared to that of normal mucosa from the same individual. Excessive or inappropriate sialylation does not appear to be responsible for the reduced BG antigen reactivity of the tumors. In fact, TCCs (9 cases) had significantly reduced sialic acid content compared to normal bladder mucosae (6 cases) regardless of their A, B, H reactivity and neuraminidase did not change their reactions for BG antigens. In addition, spontaneous unmasking of the Thomsen-Friedenreich (T) antigen was observed in invasive tumors that were negative for the expected BG antigen(s). Tumors from patients of blood group A or B often showed increased reactivity for the H antigen, although their A or B antigen was reduced or absent. In view of the known biosynthetic sequence from H to A and B substances, these observations suggest a specific biochemical defect in the tumors.