| Metastasis and postoperative recurrence are the biggest obstacles to improve the postoperative long-term survival in patients with hepatocellular carcinoma (HCC), so the molecular mechanisms of metastasis have been becoming the key points in the research of HCC. Recent studies showed that neovascularization was one of the most important mechanisms of metastasis of HCC. The role of genes and proteins associated with neovascularization in the metastasis and postoperative recurrence of HCC have become the "hot points" in the study of HCC.Up to date, the most potent growth factor of endothelium is vascular endothelial growth factor (VEGF), which plays important roles in the regulation of metastasis of malignancy. However, the relationships between the expression of VEGF in HCC and the biological behavior and prognosis of HCC have not been clarified. The signal transduction pathways of VEGF in hepatoma cells have not been clarified too. Settlement of the two problems are not only very important for the investigation of mechanisms of metastasis of HCC, but also important for selection of efficacious new drugs to suppress the angiogenesis in malignancy to prevent the metastasis.This study is designed to investigate the expression of VEGF, hypoxia-inducible factor 1 alpha (HIF-1a) and epidermal growth factor (EGF) and to analysis the relationship between their expressions and the biological behaviors and prognosis of HCC. Also the relationship between the hypoxia or EGF and the overexpression of VEGF and the signal transduction pathway of VEGF transcription in hepatoma cells were studied.PART 1 Expression of VEGF, HIF-1 alpha and EGF in hepatocellular carcinomaPurposes: To investigate the expressions of VEGF , HIF-1 a and EGF in HCC and the relationships between the expressions of VEGF, HIF-1 a and EGF with the biological behaviors and prognosis of HCC.Materials and methods: The expressions of VEGF, HIF-1 a and EGF in 36 samples of HCC and their corresponding paraneoplastic tissues and 6 samples of normal liver tissues were studied by usage of immunohistochemistry assay. The relationship between the expressions of VEGF, HIF-1 a and EGF with the clinicopathologic parameters, neovascularization and prognosis and the correlations among the expressions of VEGF, HIF-1 a and EGF were analysised.Results: The expressions of VEGF of HCC were positive in 32 cases. The positive rate was 88.9% (32/36), which was significantly higher than that in paraneoplastic tissue and normal liver tissue (PO.05). The expression of HIF-1 a and EGF in HCC tissue were 66.7% and 75.0% respectively, both higher than those in paraneoplastic tissues and normal liver tissues (PO.05). The expression of VEGF and HIF-1 a in HCC with microscopic venous invasion weresignificantly higher than those in HCC without microscopic venous invasion (P<0.05). The I, 2-year survival rates were both 100% in VEGF negative HCC group, 86.7% and 21.7% in VEGF weak positive group, 54.0% and 0 in VEGF strong positive group. The differences of the survival rates among the three groups were significant (P<0.05). The 1, 2-year survival rates were 100% and 60.0% in EGF negative HCC group, both 70.0% in EGF weak positive group and 27.1% and 0 in EGF strong positive group. The differences of the survival rates among the EGF negative group, weak positive group with strong positive group were significant (P<0.05).Spearman correlation analysis did not only show the expression of HIF-1 a was correlated with the expression of VEGF (rs=0.459, P<0.01), but also the expression of EGF was correlated with the expression of VEGF(rs=0.462, P<0.01) .Conclusions: Overexpression of VEGF, HIF-1 a and EGF are presented in HCC. The expressions of VEGF and EGF in HCC were not only correlated with the malignant behaviors including neovascularization and venous invasion, but also with the poor prognosis of HCC. The expression of HIF-1 a in HCC was also asssociated with the microscopic venous invasion. The expressions of HIF-1 a and EGF were correlated with the overexpressi...
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