Study on Correlation between the Expression of P-Glycoprotein and the Effect of Chemotherapy in Transitional Cell Carcinoma / 대한비뇨기과학회지

ABSTRACT

The resistance of neoplastic cells to chemotherapeutic agents may develops by a variety mechanisms. One of these mechanisms seems to be the amplification or overexpression of the multidrug resistance(MDR) gene. The MDR phenotype is conferred by a 170kD membrane protein, P-glycoprotein. This protein acts as a drug efflux pump for a variety of structurally unrelated antineoplastic agents, especially hydrophobic natural products such as adriamycin and vincristine. In the present study, immunohistochemical stain for P-glycoprotein was performed in paraffin section of 41 specimens of transitional cell carcinoma of the bladder obtained prior to chemotherapy to investigate the usefulness of P-glycoprotein as a predictor of response to M-VAC ( methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy. The overall clinical response rate to chemotherapy was 65.9%. The overall 3- year survival rate was 63%, with 80% in responder group( clinical complete and partial remission) and 36.3% non-responder group(minor response, stabilization and progression ) (P<0.05). In the responder group, 7.4% expressed strongly positive P-glycoprotein, 63% weakly positive and 29.6% negative. In the non-responder group, 28.6% expressed strongly positive P-glycoprotein, 64.3% weakly positive and 7.1% negative. The negative expression rate was high in responder group than non-responder, but this difference was not statistically significant. There was no correlation of expression of P-glycoprotein with either tumor stages or grades. In conclusion, these results suggest that tumors with negative expression of P-glycoprotein seem to have a better clinical response to chemotherapy, and further investigation of other mechanisms of cellular drug resistance should be required.