Investigation of GST and drug resistance protein expressions in relation to chemotherapy in breast cancer

Abstract

Background. During cancer therapy, resistance to chemotherapeutic agents is common and often linked to multidrug resistance mechanisms. Glutathione S-transferases (GSTs) and ATP-binding cassette (ABC) transporters, including multidrug resistance (MDR) proteins, multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP), are implicated in drug resistance. Material and methods. Protein expressions were determined in the tumor and surrounding tumor free breast tissues of 145 breast cancer patients by immunohistochemistry technique. Among 145 patients, 50 received preoperative (neoadjuvant) chemotherapy, and 95 received postoperative (adjuvant) chemotherapy. Results. In 50 neoadjuvant breast cancer patients, GSTA1, GSTK1, GSTM1, GSTO1, GSTP1, GSTS1, GSTT1, GSTZ1, MDR1, MRP1, MRP2, MRP3, MRP7, and BCRP expressions were higher in tumor epithelium compared to normal epithelium (p<0.05). In 95 adjuvant breast cancer patients, GSTA1, GSTK1, GSTM1, GSTP1, GSTT1, GSTZ1, MDR1, MRP1, MRP2, and MRP3 expressions were higher in tumor epithelium than in normal epithelium (p<0.05). GSTP1, GSTT1, and MRP3 expressions were significantly higher in neoadjuvant compared to adjuvant-treated breast cancer patients’ tumor tissues (p<0.05). Conclusions. GSTP1, GSTT1, and MRP3 may be important in inactivating the chemotherapeutic agents used in platinum-based treatment and are thus responsible for the drug resistance in breast cancer patients.