BIOLOGICAL MARKERS IN TRANSURETHRAL BIOPSIES FROM BLADDER-CANCER - PRELIMINARY-RESULTS

A biologic profile including proliferative.activity, evaluated as H-3- thymidine labeling index (H-3-dT LI), DNA ploidy, p53 tumor-suppressor gene and P-glycoprotein (P-170), as an expression of the multidrug re sistance gene, was defined for 50 primary transitional cell carcinomas of the bladder. H-3-dT LI was evaluated by autoradiography on histolo gic sections after incubation of fresh tumor biopsies with H-3-thymidi ne. Ploidy was defined by flow cytometric analysis of DNA content on n uclei suspensions obtained from frozen material. Expression of p53 pro tein and P-170 glycoprotein was detected by immunohistochemistry using the PAb1801 and C219 monoclonal antibody respectively, on sections fr om paraffin-embedded tumor biopsies. Invasive tumors showed a higher m edian H-3-dT LI (12.7% vs 4.2%) and a higher frequency of aneuploidy ( 73% vs 43%) and more frequently expressed p53 (82% vs 36%) than superf icial tumors. Further analysis showed that proliferative activity was higher in invasive than in superficial cancers only in p53-positive or aneuploid tumors and not in p53-negative or diploid tumors. Moreover, proliferative activity and p53 overexpression, but not ploidy, were d irectly related to histologic grading and tumor stage. Generally, P-17 0 was not significantly related to any biologic or clinico-pathologic factor. Kinetic and phenotypic biologic markers are differently relate d to clinico-pathologic factors. A panel of biologic features can be e asily evaluated on small transurethral biopsies at diagnosis, during e ndocavitary treatment or follow-up in bladder cancer patients.