Correlation between the expression of P-glycoprotein and multidrug-resistant phenotype in transitional cell carcinoma of the urinary tract.
The expression of a multidrug-resistant (MDR) gene product, P-glycoprotein, was examined immunohistochemically in 41 transitional cell carcinomas (TCCs) of the urinary tract. In 23 of these, chemosensitivity to adriamycin (ADM) and vinblastine (VBL) was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and MDR phenotype was investigated. P-glycoprotein was detected in 13 (72.2%) of the 18 untreated TCCs of the upper urinary tract (UUT), 6 (31.6%) of the 19 untreated TCCs of the bladder, and all of the 4 TCCs treated with M-VAC chemotherapy, respectively. Fourteen (87.5%) of the 16 TCCs with a positive expression of P-glycoprotein were resistant to ADM and VBL, whereas all of the 4 TCCs sensitive to both drugs were negative in the expression of P-glycoprotein. The succinate dehydrogenase activity of TCCs with a positive expression of P-glycoprotein was significantly higher than that of TCCs with a negative expression of P-glycoprotein (P < 0.05). Thus, there was a good correlation between the expression of P-glycoprotein and MDR phenotype in the chemosensitivity test. These results suggest that intrinsic MDR exists in some TCCs of the urinary tract, particularly UUT, and that the immunohistochemical investigation of P-glycoprotein may be useful for predicting the MDR phenotype in TCCs of the urinary tract.
Naito
S
S
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Sakamoto
N
N
Kotoh
S
S
Goto
K
K
Matsumoto
T
T
Kumazawa
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D010641:Phenotype; D014571:Urologic Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014747:Vinblastine / Q000494:pharmacology / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D014747:Vinblastine; D004317:Doxorubicin