Neoangiogenesis and expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor, and glucose transporter-1 in endometrioid type endometrium adenocarcinomas.
OBJECTIVE
Hypoxia Inducible Factor-1alpha (HIF-1alpha) is a transcriptional factor that activates multiple genes including Vascular Endothelial Growth Factor (VEGF) and glucose transporter-1 (GLUT-1) in response to hypoxia and promotes neoangiogenesis.


METHODS
Expression of HIF-1alpha VEGF, and GLUT-1 were analyzed by immunohistochemistry and microvessel density (MVD) was determined by CD 34 immunostaining in 100 endometrioid type endometrial adenocarcinoma, FIGO Stages I-IV.


RESULTS
High expression of HIF-1alpha, VEGF and GLUT-1 were significantly more prevalent in advanced stages than early stages (p<0.001). High expression of HIF-1alpha was found in 100% of Stage III-IV patients, whereas 50% of Stage II and 9% of Stage I patients had high HIF-1alpha expression. Similarly, high VEGF expression was determined in 4% of Stage I and 30% of Stage II patients, however 90% of Stage III-IV patients had high expression of VEGF. Comparing the GLUT-1 scores, it was found that increasing stages correlated with high GLUT-1 expression. Additionally, a statistically significant difference was also noted in MVD between stages (p<0.001). The average MVD of Stage I patients was 31.87+/-7.73. It was found 49.24+/-7.60 in Stage II, and 78.74+/-14.48 in Stage III-IV patients. On analyzing expression of HIF-1alpha, VEGF and GLUT-1 and MVD in pairs, statistically significant correlations were found between each other (p<0.001).


CONCLUSIONS
HIF-1alpha was increasingly expressed from early stages through advance stages of endometrioid adenocarcinoma, paralleled by activation of its downstream genes such as GLUT-1, VEGF and increased angiogenesis. These results highlight the importance of hypoxia and related pathways in progression of endometrial carcinoma.
Ozbudak
Irem Hicran
IH
Department of Pathology, University of Akdeniz School of Medicine, Antalya, Turkey. iremhicrang@hotmail.com
Karaveli
Seyda
S
Simsek
Tayyup
T
Erdogan
Gulgun
G
Pestereli
Elif
E
D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A