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 multidrung 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 vincristinge.
In the present study, immunohistochemical stain for P-glycoprotein was performed in paraffin section of 41 specimens of transitional cell carcinoma of the bladder obatined prior to chemotherapy to in vestigate the usefulnes of P-glycoprotein as a
predictor of response to M-VAC (Methoteexate, 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.
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