Erythropoietin receptor and tissue factor are coexpressed in human breast cancer cells.

Abstract Erythropoiesis-stimulating agents (ESAs) are recommended for treating chemotherapy-induced anemia in breast cancer patients. Reduced survival rates in ESAs-treated patients have been reported, possibly due to thromboembolic complications, however the exact mechanism remains obscure. The principal activator of blood coagulation in cancer is tissue factor (TF). There are data that erythropoietin receptor (EPO-R) is expressed in tumor cells. The purpose of this study was to evaluate the expression of EPO-R and TF in loco in breast cancer. The expression of EPO-R and TF was investigated in 24 invasive breast carcinoma specimens. Immunohistochemical (IHC) methodologies according to ABC technique and double-staining IHC procedure were employed utilizing antibodies against EPO-R and TF. Expression of EPO-R and TF was demonstrated in the tumor cells in all breast cancer specimens. No staining for EPO-R and TF was visualized in normal breast tissue. Double staining studies revealed co-expression of both EPO-R and TF in breast cancer cells and endothelial cells. EPO-R and TF expression and their coexpression in breast cancer cells suggest a possibility that EPO-R might be responsible for some adverse effects and reduced survival observed in ESAs-treated breast cancer patients with anemia, possibly due to the interaction with TF. Further experimental studies are warranted to determine the role of both EPO-R and TF in the treatment with ESAs of breast cancer patients with chemotherapy-induced anemia.