Abstract
Chemotherapy is commonly used for the treatment of breast cancer. However, the resistance to chemotherapeutic agents, often mediated by multidrug resistance (MDR) mechanisms, is a common occurrence. The present study examined the expression of several MDR-related proteins (MRPs) in invasive ductal carcinoma (IDC) of the breast, and assessed their association with clinicopathological variables and their prognostic significance. In addition, immunohistochemistry was used to measure the expression of MRP, p-glycoprotein (P-gp), topoisomerase 2α (Topo2α), thymidylate synthase (TS) and glutathione-S-transferase π (GST-π) in 156 resected IDCs of the breast. Pearson’s χ2 test and Spearman’s correlation coefficient were used to analyze the association between MDR protein expression and several clinicopathological variables. The association between each of the five MDR proteins was also examined. Furthermore, Kaplan-Meier analysis and Cox regression modeling were used to assess overall survival. The expression of MRP, P-gp, Topo2α, TS and GST-π was detected in 20.5% (32/156), 25.0% (39/156), 84.0% (131/156), 41.7% (65/156) and 41.0% (64/156) of cases examined, respectively. No correlation was identified between MRP and Topo-2α and the clinicopathological variables examined. By contrast, P-gp (χ2=20.226; P<0.0001) and GST-π (χ2=35.032; P<0.0001) were found to positively correlate with tumor grade. In addition, staining for TS was associated with axillary lymph node metastasis (χ2=42.281; P<0.0001). The expression levels of P-gp and GST-π were found to be significantly correlated (r= 0.319; P<0.0001). Furthermore, GST-π expression was elevated in estrogen receptor-negative breast cancer (χ2=17.407; P<0.0001). Tumor histological grade, in addition to TS and GST-π expression, were significant predictors of a poor survival outcome. TS and GST-π are consequently useful prognostic biomarkers in IDC, therefore, when establishing a personalized chemotherapeutic plan, the expression of MDR proteins must be considered.
Highlights
Invasive ductal carcinoma (IDC) of the breast is a malignant disease, which affects numerous females worldwide [1]
multidrug resistance (MDR) is a common mechanism by which tumor cells become resistant to numerous chemotherapeutic agents
While this MDR response is multi‐faceted, it typically involves the upregulation of several key proteins that promote the efflux of drugs out of tumor cells, decreasing their biological efficacy
Summary
Invasive ductal carcinoma (IDC) of the breast is a malignant disease, which affects numerous females worldwide [1]. Despite its success, resistance to chemotherapeutic agents is a common occurrence that is often attributable to mechanisms of multidrug resistance (MDR) [3,4]. Proteins that mediate this resistance mechanism have been identified and have the potential to serve as biomarkers or prognostic indicators of outcome, the function of these MDR‐related proteins (MRPs) in IDC of the breast has not been extensively investigated. Resistance is achieved by an increased efflux of chemotherapeutic agents out of the tumor. This is an acquired problem, as while certain tumors are initially responsive, they become resistant following prolonged treatment. Tumors fail to respond to therapy at all, a mechanism known as de novo resistance [5]
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