MRP AND MDR1 GENE-EXPRESSION IN PRIMARY BREAST CARCINOMAS

To evaluate the clinically important mechanisms of drug resistance in breast cancer, the expression of the MRP gene and the corresponding on e for the MDR1 gene were determined in primary breast carcinoma specim ens by both reverse transcription-PCR (n = 134) and immunohistochemist ry (n = 63), Expression of MRP RNA was observed in all breast cancer s pecimens, MDR1 RNA was detected in 80 (60%) of the carcinomas, Stainin g with monoclonal antibodies QCRL-1 and QCRL-3, which both recognize M RP, was strong in 15 (24%) and weak in the remaining 48 specimens (76% ), Staining with C219, which recognizes P-glycoprotein, was strong in 6 (9%), weak in 30 (48%), and negative in 27 (43%) of the samples, Str ong MRP staining was more frequent in T-3 and T-4 tumors than in T-1 a nd T-2 tumors and in the primary tumors of patients with distant metas tases but was independent of age, menopausal status, histology, histol ogical grade, estrogen receptor, progesterone receptor, and lymph node involvement, No correlation between MRP staining and expression of MD R1 RNA or P-glycoprotein was observed, Thus, these results indicate ex pression of both the MRP gene and the MDR1 gene in primary breast carc inomas and suggest that clinical drug resistance in breast cancer is m ost likely multifactorial.