High expression levels of erythropoietin and its receptor are not correlated with shorter survival in human glioblastoma

Abstract

Abstract. Erythropoietin (EpO) is used to treat anemia in neoplastic disease. EpO also exerts neuroprotective effects on neuronal cells, making a prophylactic use against the neurocognitive effects of radiochemotherapy probable. however, EpO/ EpO-receptor (EpOr) signalling has been also detected in glioblastoma cells. data collected in vitro and in vivo show conflicting results on the effect of EPO on malignant gliomas. the association between EpO and EpOr expression and the prognosis of human glioblastomas was analyzed. probes of human glioblastomas with complete documentation of clinical course and treatment were assessed by immunohistochemistry for the expression of EpO and EpOr (n=80). using univariate and multivariate survival analysis, the association with age, gender, radiation, chemotherapy and extent of resection was determined. high levels of EpOr were correlated with a median survival advantage of 7 months (p<0.01). By univariate, but not multivariate, analysis, high levels of EpO and EpOr were associated with a significant prolongation of 7 months median survival when compared to low levels of both molecules. in patients treated with radiochemotherapy adjuvant to surgery, the median survival was 6.5 months longer in patients with high levels of EpOr (p<0.04). according to previous studies, longer patient survival is associated with EpOr expression. therefore, EpO appears to be safe for the treatment of anemia in glioblastoma patients. Ηowever, a prophylactic use, i.e., for neuroprotection, is not recommended in light of the functional studies described in the literature.

The effect of erythropoietin on normal and neoplastic cells

“…However, analysis of the Henke et al clinical samples indicated that the level of EpoR protein expression suggested by the C-20 staining did not correlate with the level of Epo R mRNA 230. In addition, not all groups reported correlations between C-20 antibody staining of other clinical tumor specimens and adverse clinical events 243–246. Further, in cells deemed to be EpoR-positive through staining with C-20 antibody, no cellular responses, such as changes in proliferation or viability, were observed 247.…”

“… 230 In addition, not all groups reported correlations between C-20 antibody staining of other clinical tumor specimens and adverse clinical events. 243 – 246 Further, in cells deemed to be EpoR-positive through staining with C-20 antibody, no cellular responses, such as changes in proliferation or viability, were observed. 247 These discordant results were highlighted in a study in which tumor cells from patients with B-CLL were reported to express EpoR using a nonspecific anti-EpoR antibody, but no EpoR protein was detected on the cell surface using a more specific digoxigenin-labeled rHuEpo binding method.…”