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.
Benson
M C
MC
Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York.
Giella
J
J
Whang
I S
IS
Buttyan
R
R
Hensle
T W
TW
Karp
F
F
Olsson
C A
CA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D002460:Cell Line; D002648:Child; D004351:Drug Resistance; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins