Expression of the MAGE-1 gene in human hepatocellular carcinomas.
OBJECTIVE: To further investigate the expression of MAGE-1 gene in hepatocellular carcinoma (HCC). METHODS: The tumors and adjacent liver tissue from 45 HCC patients and liver tissue from 28 non-HCC patients (16 with liver cirrhosis and 12 with normal liver) were characterized by RT-PCR. A 421 bp PCR product from a cDNA fragment spanning exons 1, 2 and 3 was sequenced. The HLA type was assayed by standard ELISA in 43 HCC patients. RESULTS: Thirty-two of 45 tumor tissues from HCC patients expressed MAGE-1 mRNA (71.1%). In contrast, MAGE-1 mRNA was not detected in adjacent tissues. Three were found to have point mutations at 3 identical sites resulting in the substitution of two amino acid residues. The most frequent HLA types in 43 HCC patients were: HLA-A2, 53.5%; A11, 25.6%; A24, 20.9%; A33, 20.9%; HLA-B13, 28.3% and B35, 23.2%. Expression of HLA-A33 (20.9%) was higher in HCC patients than that predicted in the normal Chinese population (8.8%). There was no discemable correlation between MAGE-1 expression and alpha-FP level, tumor size and hepatitis B or C virus infection. The identification of peptides which are restricted by haploptypes other than A1 should increase the opportunity for peptide based immunotherapy. CONCLUSIONS: This study shows that MAGE-1 mRNA is highly expressed in HCC tumor tissue in Chinese patients. Previously unreported point mutations in the MAGE-1 gene are described and may also provide additional opportunities for immunotherapy.