The clinicopathological significance of heparanase and basic fibroblast growth factor expressions in hepatocellular carcinoma

Heparan sulfate plays an essential role for insolubility of the components of extracellular matrix and represents a storage depot for various growth f actors. Therefore, heparanase produced by a given tumor may facilitate tumo r invasiveness and angiogenesis through the release of heparan sulfate-boun d growth factors. Although the growth factors responsible for angiogenesis in hepatocellular carcinoma (HCC) have recently been investigated, the clin icopathological significance of heparanase in connection with basic fibrobl ast growth factor (bFGF) expression in HCC has not been evaluated so far. Fifty-five patients who had undergone hepatic resection for HCC without pre operative treatment were included in the present study. Expression of hepar anase mRNA was evaluated by reverse transcription-PCR, and bFGF was examine d by Western blotting using a monoclonal antibody, Tumor angiogenesis was e valuated by immunostaining with a factor Vm-related monoclonal antibody. Ex pression of heparanase mRNA was detected in 47% of HCCs and was significant ly correlated with larger tumor size (P = 0,01), presence of portal vein in vasion (P = 0,01), and higher overall tumor invasiveness (P = 0,02), Moreov er, its expression was correlated with tumor microvessel density (MVD; P = 0,02), There was a direct correlation between the levels of bFGF proteins a nd MVD in HCCs (P = 0,0001), and, furthermore, concomitant expression of bF GF and heparanase was associated with higher tumor MVD as compared with exp ression of either factor alone (P = 0,01). In conclusion, the expression of heparanase in HCC enhances growth, invasio n, and angiogenesis of the tumor, and bFGF seems to be a potent angiogenic factor for HCC.