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.