FLOW CYTOMETRIC DETERMINATION OF THE MULTIDRUG RESISTANT PHENOTYPE IN TRANSITIONAL CELL-CANCER OF THE BLADDER - IMPLICATIONS AND APPLICATIONS

We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy.