CLINICAL-SIGNIFICANCE OF THE INCREASED MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) GENE-EXPRESSION IN PATIENTS WITH PRIMARY BREAST-CANCER

The efficacy of cancer treatment is limited by either intrinsic or acq uired resistance to various chemotherapeutic agents. To evaluate the c linically important factors related to prognosis in primary breast can cer retrospectively, we investigated the expression of the following g enes involving acquirement of drug resistance: multidrug resistance I (MDR1), multidrug resistance-associated protein (MRP), and topoisomera se (Topo) I, II alpha, and II beta. Using an RT-PCR method, we semiqua ntified the gene expression level in untreated stage II breast cancer tissue (n = 27) and noncancerous breast tissue (n = 10). Among the 27 cancer patients, who were all treated by adjuvant chemoendocrine thera py after surgery, 10 patients showed relapse within the following 10 y ears whereas 17 patients did not. The gene expression levels of MDR1, MRP, and Topo I, II alpha, and II beta were normalized to the level of the beta 2-microglobulin RT-PCR product. MRP mRNA expression was dete cted in 70% of the breast cancer tissues and its expression levels wer e significantly increased in the cancer group compared with the noncan cerous breast tissues. Furthermore, the MRP level was much higher in t he relapsed patient group. On the other hand, there were no significan t differences in the MDR1 mRNA levels between the noncancerous and can cer groups. Although Topo II alpha mRNA was not detected in noncancero us breast tissues, it was detected in 52% of the breast cancer tissues . In cancer patients, no significant difference in Tape II alpha mRNA levels was observed between the relapsed and nonrelapsed groups. These findings suggest that MRP might be used as one of the markers for poo r prognosis in patients with breast cancer.