Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in hepatocellular carcinoma: Impact on neovascularization and survival.
OBJECTIVE
To study the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival.


METHODS
Expressions of HIF-1alpha, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1alpha and VEGF with the clinicopathological data and survival are analyzed.


RESULTS
The positive rate of VEGF in HCC was 32/36, which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of HIF-1alpha in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of VEGF and HIF-1alpha in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P<0.05). Spearman correlation analysis does not only show the expression of HIF-1alpha as correlated with the expression of VEGF (r(s) = 0.459, P<0.01), but it also shows the expression of HIF-1alpha and VEGF as correlated with MVD (r(s) = 0.412 and 0.336, respectively, P<0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P<0.05), whereas the differences of the survival rates among the HIF-1alpha negative group and positive group are not significant (P>0.05).


CONCLUSIONS
HIF-1alpha plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.
Huang
Geng-Wen
GW
Department of General Surgery and Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China. huanggengwen@yahoo.com.cn
Yang
Lian-Yue
LY
Lu
Wei-Qun
WQ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A