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.