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.
Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York.
M C
MC
Benson
J
J
Giella
I S
IS
Whang
R
R
Buttyan
T W
TW
Hensle
F
F
Karp
C A
CA
Olsson
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