ALTERATIONS OF ONCOGENES, TUMOR-SUPPRESSOR GENES AND GROWTH-FACTORS IN HEPATOCELLULAR-CARCINOMA - WITH RELATION TO TUMOR SIZE AND INVASIVENESS

Objective To make a better understanding of the molecular mechanisms i nvolved in recurrence and metastasis of the hepatocellular carcinoma ( HCC), some invasion related oncogenes, and growth factors have been in vestigated. Methods The studies were separately carried out, the resul ts of which were summarized in this article with relation to tumor siz e and invasiveness of HCC. Results The aberration rates of p53 and CDK N2 in HCC were 45.9% and 36.4% respectively, which were higher in inva sive HCC compared with non-invasive HCC. H-ras expression was positive in 29.3% of HCC, which was associated with recurrence and extrahepati c metastasis of HCC. Intralesional injection of H-ras antisense gene m arkedly inhibited the tumor growth and metastasis of HCC in nude mice. The positive rates of transforming growth factor (TGF)-alpha, epiderm al growth factor receptor (EGFR) and c-erbB-2 were 45.7%, 47.1% and 92 .3% respectively. The expression of EGFR was closely related to TGF-al pha, which was related to HCC recurrence. But no obvious difference of TGF-alpha or c-erbB-2 expression was found between HCC with and witho ut recurrence, or with and without extrahepatic metastasis. Expression of nm23 / tissue inhibitor of metalloproteinase (TIMP)-2 was positive ly associated with the prognosis of HCC patients (Log-rank, P < 0.001) . The alterative rates of above-mentioned genes and growth factors in small HCC were slightly lower than that in large ones, but no signific ant difference was shown except the p53 mutation. Conclusions The p53/ CDKN2 mutation, overexpression of H-ras/EGFR, were associated with the invasiveness and recurrence of HCC. H-ras antisense gene might be of potential implication in the control of HCC recurrence and metastasis. Expression of nm23/TIMP-2 was closely related to the prognosis of HCC patients. Biological characteristics remained critical points to the prognosis even in small HCC.