Erythropoietin receptors in endometrial carcinoma as related to HIF1{alpha} and VEGF expression.
Erythropoietin receptors (EpoRs) are expressed in a large percentage of cells in many human malignancies, including endometrial adenocarcinoma. In such tumors, administration of recombinant human erythropoietin (rhEpo) during radiotherapy and chemotherapy may oppose tumor progression by interfering with growth and invasion pathways. In the present study, a strong EpoR expression was demonstrated in 58.8% of 72 stage I endometrial adenocarcinomas, and this pattern was linked with a high degree of tumor differentiation (p=0.01), deep myometrial invasion (p=0.04) and, marginally, with poor prognosis (p=0.06). In addition, a strong association with the immunohistochemical expression of hypoxia-inducible factor 1alpha (HIF1alpha) and the downstream angiogenic protein vascular endothelial growth factor (VEGF) was noted. In multivariate analysis, HIF1alpha, but not EpoR, was associated with the depth of myometrial invasion (p=0.04) and marginally with prognosis (p=0.07). It is concluded that EpoR are common constituents of endometrial adenocarcinomas and are related to tumor aggressiveness, although this is probably a result of their involvement in an active HIF pathway.
Department of Pathology, Democritus University of Thrace, Greece. targ@her.forthnet.gr
Alexandra
A
Giatromanolaki
Aliki
A
Fiska
Dimitra
D
Pitsiava
George
G
Kartalis
Michael I
MI
Koukourakis
Efthimios
E
Sivridis
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017467:Receptors, Erythropoietin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A