M. Mise et al., CLINICAL-SIGNIFICANCE OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AND BASICFIBROBLAST GROWTH-FACTOR GENE-EXPRESSION IN LIVER TURNER, Hepatology, 23(3), 1996, pp. 455-464
Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Howev
er, the relationship between the vascularity of HCC and the expression
of angiogenic factors has not been investigated. In addition, no deta
iled studies have examined the possible involvement of angiogenic fact
ors in the grade of malignancy of HCC. The aim of this study was to de
termine which angiogenic factors regulate tumor angiogenesis and contr
ibute to the invasive ability of liver tumors, especially of HCC. Nort
hern blot analysis was used to examine the transcriptional expression
of vascular endothelial growth factor (VEGF), basic fibroblast growth
factor (FGF), and acidic FGF in resected surgical specimens (20 HCC an
d 9 metastatic liver tumors). Correlations between messenger RNA (mRNA
) expression and arteriographic findings, as well as histopathological
findings, were evaluated. Immunohistochemistry was performed to ident
ify the localization of cells expressing VEGF in HCC. Higher levels of
VEGF mRNA were observed in 12 of 20 HCC and in 2 of 9 metastatic live
r tumors than in corresponding nontumorous tissues, The degree of VEGF
mRNA expression was significantly correlated with the intensity of tu
mor staining in angiograms (P < .01). On immunohistochemical observati
on, VEGF protein was intensely detected in HCC cells. Furthermore, bas
ic FGF mRNA was detected in 9 of 20 HCC and was related to the capsula
r infiltration of cancer cells (P < .05). In contrast, no significant
difference was observed in the very low levels of acidic FGF mRNA foun
d in the tumorous and nontumorous portions of the Liver. In conclusion
, these results suggest that VEGF contributes to angiogenesis of liver
tumors, whereas basic FGF may be involved in the invasion of HCC into
the surrounding tissues.