Different gene expression of MDM2, GAGE-1, -2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia

Overexpression and/or mutations of oncogenes, tumour suppressor genes and t umour rejection genes have been observed in several human malignancies. The ir analyses might be of diagnostic importance. Therefore, malignant hepatoc ytes derived from hepatocellular carcinoma (HCC) tissue as well as non-mali gnant hepatocytes derived from focal nodular hyperplasia (FNH) were studied . Samples containing normal human hepatocytes (HC) served as controls. Cell ular material was obtained by fine-needle aspiration biopsy guided by ultra sound. Cells were analysed for expression and mutation of the oncogene MDM2 , the genes GAGE-1, -2 coding for tumour-associated antigens and the candid ate tumour suppressor gene FHIT. Different patterns of non-mutant FHIT tran scripts including precise deletion of exons were found in 7/10 HCC, 2/10 FN H and 2/10 HC. However, expression of non-mutant GAGE-I, -2 RNA was demonst rated exclusively in 6/10 HCC samples. Further genetic features specific of HCC were point mutations in a zinc-finger motif of MDM2 (3/10 HCC samples) . Neither GAGE-1, -2 expression nor MDM2 mutations were observed in the FNH samples, or in normal hepatocytes. Our findings suggest that occurrence of variable FHIT transcripts is not restricted to hepatic malignant tumours. In contrast, MDM2 mutations and GAGE-1, -2 expression were associated with HCC specimens. Therefore, the RT-PCR assays for GAGE-1, -2 and MDM2 might b e useful adjuncts in cytodiagnosis of liver neoplasms.