Hypoxia inducible factor 1 alpha and 2 alpha expression is independent of anemia in patients with stage I endometrial cancer.
OBJECTIVE
To investigate whether anemia, a putative factor counteracting the efficacy of radiotherapy, up-regulates the endogenous markers of intratumoral hypoxia, the hypoxia inducible factors HIF1 alpha and HIF2 alpha.


METHODS
Forty-two hysterectomy specimens harboring endometrial adenocarcinomas of the endometrioid cell type, stage I were investigated immunohistochemically for the expression of HIF1 alpha, HIF2 alpha and the down-stream inducible expression of vascular endothelial growth factor VEGF. The results were correlated with hemoglobin (Hb) levels.


RESULTS
There was no significant association between Hb levels and the expression of HIF1 alpha, HIF2 alpha or VEGF in our material.


CONCLUSIONS
Activation of hypoxia pathways is an intrinsic self-regulated process, independent of Hb levels in endometrial adenocarcinomas. Other factors such as microvessel density (MVD), vessel/tumor cell distance or genetic events may be important.
Koukourakis
M I
MI
Departments of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis 68100, PO Box 12, Greece. targ@her.forthnet.gr
Giatromanolaki
A
A
Liberis
V
V
Sivridis
E
E
D000230:Adenocarcinoma / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000740:Anemia / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins; D016889:Endometrial Neoplasms / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D009367:Neoplasm Staging; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D016228:Endothelial Growth Factors; D006454:Hemoglobins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D015534:Trans-Activators; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human