Clinical Significance of Multi-Drug Resistance Associated Protein and P-Glycoprotein in Patients with Bladder Cancer

Abstract

The clinical significance of multi-drug resistant proteins, such as multi-drug resistance associated protein and P-glycoprotein, in terms of prognostic value was determined in patients with bladder cancer. The expression of multi-drug resistance associated protein and P-glycoprotein was investigated immunohistochemically before and after chemotherapy. The relationship between expression of these multi-drug resistant proteins and clinical outcome assessed by tumor recurrence rate, cystectomy rate and 5-year survival rate was also investigated in 33 patients with bladder cancer. Before chemotherapy multi-drug resistance associated protein expression was observed in 1 of 28 patients (4%) while P-glycoprotein expression was observed in 22 of 33 (67%). Multi-drug resistance associated protein induction by chemotherapy was observed in 6 of 28 patients (21%), whereas P-glycoprotein induction was noted in 4 (14%). Multi-drug resistance associated protein in this disease is induced more frequently by high dose (more than 300 mg.) than low dose (less than 300 mg.) anthracyclines (p < 0.01). Immunohistochemical analysis also revealed co-expression of multi-drug resistance associated protein and P-glycoprotein in 5 of 28 patients (18%) after chemotherapy. However, there was no significant correlation between positive P-glycoprotein expression before chemotherapy and clinical outcome. Multi-drug resistance associated protein as well as P-glycoprotein mediated multi-drug resistance may be induced after chemotherapy for bladder tumors. However, the presence of P-glycoprotein before chemotherapy does not predict clinical outcome in patients with bladder cancer.