Expression of multidrug resistance protein P-glycoprotein in correlation with markers of hypoxia (HIF-1α, EPO, EPO-R) in invasive breast cancer with metastasis to lymph nodes

INTRODUCTION: Overexpression of the mdr-1 gene is the earliest discovered mechanism of multidrug resistance, which is associated with P-glycoprotein (P-gp) – a cell membrane protein responsible for the efflux of drugs of various structures out of cancer cells. Although the expression of P-glycoprotein has been demonstrated in many cancer types, its relation to markers of hypoxia such as HIF-1α, EPO-R or EPO in invasive breast cancer is not well established. The aim of this research was to analyze the co-expression of P-glycoprotein and the markers of tissue hypoxia HIF-1α, EPO, and EPO-R by immunohistochemistry in invasive breast cancer classified according to the presence of steroid receptors and the HER2 receptors. MATERIAL AND METHODS: Tissue samples were collected from 58 patients with the diagnosis of invasive breast cancer with lymph node metastases. The expression of P-gp, HIF-1α, EPO-R and EPO was determined by immunohistochemistry. RESULTS: Of all the invasive breast cancers with lymph node metastases, 15.5% expressed P-gp in cell membrane and tumor blood vessels. In our research, there was a significant positive correlation between HER2-positive tumors that did not express steroid receptors (ER–/PR–/HER2+), and P-gp expression (p = 0.049, r = 0.105). Moreover, there was a significant positive correlation between EPO expression and P-gp (p < 0.001, r = 0.474), and between HIF-1α expression and P-gp (p = 0.00475, r = 0.371). CONCLUSIONS: We found that HIF-1α and EPO expression is significantly associated with P-gp expression in invasive breast cancer with lymph node metastases. An important result of our study is the demonstration of a correlation between P-gp expression and patients with HER2-positive breast tumors that do not express steroid receptors.