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 acquired resistance to various chemotherapeutic agents. To evaluate the clinically important factors related to prognosis in primary breast cancer retrospectively, we investigated the expression of the following genes involving acquirement of drug resistance: multidrug resistance 1 (MDRl), multidrug resistance-associated protein (MRP), and topoisomerase (Topo) I, II alpha, and II beta. Using an RT-PCR method, we semiquantified 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 therapy after surgery, 10 patients showed relapse within the following 10 years whereas 17 patients did not. The gene expression levels of MDRl, 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 detected in 70% of the breast cancer tissues and its expression levels were significantly increased in the cancer group compared with the noncancerous breast tissues. Furthermore, the MRP level was much higher in the relapsed patient group. On the other hand, there were no significant differences in the MDRl mRNA levels between the noncancerous and cancer groups. Although Topo II alpha mRNA was not detected in noncancerous breast tissues, it was detected in 52% of the breast cancer tissues. In cancer patients, no significant difference in Topo 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 poor prognosis in patients with breast cancer.