Expression of Family A Melanoma Antigen in Human Gastric Carcinoma

Abstract

Background: Since the members of the MAGE (melanoma antigen) gene family have been reported to be expressed in tumor cells but not in normal tissues, they have been considered as targets for tumor-specific immunotherapy. Materials and Methods: The expression pattern of MAGE-A genes and their expression mechanisms were investigated in 10 gastric cancer cell lines and 1,097 gastric carcinoma specimens by RT-PCR, IHC, Western blot and MSP. Results: MAGE-A1, -A2 and -A3 gene transcripts were detected in 1, 3 and 4 of 10 gastric cancer cell lines, respectively. In those cases in which the mRNA expression of MAGE-A2 or -A3 was detected, the promoters of the corresponding genes were hypomethylated. MAGE-A protein expression was detected in 30% (3/10) of the cell lines and 15.8% (173 out of 1,097) of the carcinoma specimens. Promoter hypomethylation of the MAGE-A2 or -A3 genes correlated with their expression in primary gastric cancer tissue and gastric cancer cell lines. MAGE-A protein expression was associated with tumor invasiveness (p=0.002), lymph node metastasis (p<0.001), advanced pathologic stage (p<0.001) and a worse prognosis (p<0.005). Conclusion: MAGE-A protein expression occurred due to promoter hypomethylation in a minor subset of gastric cancers, and MAGE-A expression increased during the progression of the gastric cancer.