Expression of erythropoietin and its receptor in neuroblastomas

BACKGROUND: Children with high-risk neuroblastomas (NB) potentially may benefit from treatment with recombinant human erythropoietin (Epo). Epo is a stimulator of erythropoiesis, acting through its receptor (EpoR). The objective of the current study was to evaluate expression levels of Epo and EpoR in NB and in normal tissues and their effects on the proliferation of tumor cells. METHODS: A tissue microarray study was performed with 101 primary tumors, 39 paired metastases, 56 paired control tissues, and 6 human NB cell lines. Immunohistochemical staining was performed using antibodies against Epo and EpoR. Immunostaining intensity was evaluated by using a semiquantitative score based on the percentage of positive cells. An in vitro analysis of cell proliferation and cell cycle in the presence of recombinant Epo was performed in the 6 cell lines. RESULTS: The expression of EpoR was found to be significantly higher in tumors than in paired control tissues (P < .0001) compared with the expression of Epo (P = .06), and the expression of EpoR was significantly higher in lymph node metastases than in paired primary tumors (P = .02) compared with Epo (P = .99). Survival analysis demonstrated that the patients who had tumors with the highest expression of EpoR had a significantly better overall survival (P = .03). In the in vitro study, recombinant Epo did not modify proliferation and cell cycle in the cell lines regardless of the EpoR expression level. CONCLUSIONS: Epo and EpoR were expressed in NB but did not modify tumor cell proliferation. The results of the current study suggested that Epo may be used safely for supportive care in children with NB.