Investigation of the expression of melanoma antigen-encoding genes (MAGE-A1 to -A6) in oral squamous cell carcinomas to determine potential targets for gene-based cancer immunotherapy

Abstract

MAGE genes are silent in normal tissues except testis but are expressed in a variety of neoplastic lesions, and therefore represent ideal targets for immunotherapy. We analysed the expression of 6 MAGE-A genes (MAGE-A1 to -A6) to determine potential implications of these antigens as targets for immunotherapy in oral squamous cell carcinoma (OSCC). Oral tumor specimens (n=21) and non-neoplastic tissue samples (n=10) of oral mucosa from healthy patients were examined by a highly sensitive reverse transcription-nested polymerase chain reaction (MAGE-1- to -6 assay) which detect any cancer cells that express at least one of six MAGE subtype genes and allows also the identification of individual MAGE isotypes (M1 to M6). MAGE expression was restricted to neoplastic specimens. No expression of MAGE was observed in the non-neoplastic normal oral mucosal tissues. Fifteen of 21 (71%) oral carcinomas expressed at least one of MAGE-A1 to -6. The expression pattern of subtypes was heterogeneous: 62% of the tumor patients were positive for MAGE-3, 57% for MAGE-4, 48% for MAGE-6, 43% for MAGE-1, 38% for MAGE-2 and 24% for MAGE-5. Also coexpression of the genes could be determined: 13 (62%) coexpressed two, 10 (48%) coexpressed three, 8 (38%) coexpressed four, 6 (29%) coexpressed five and 5 coexpressed six of the 6 subtypes tested. The high incidence of MAGE expression in oral cancer indicates that monitoring of MAGE-A subtype expression in OSCC may be of potential interest to determine new immunotherapeutic targets and may be a possibility of specific immunotherapy with polyvalent anti-genes for this disease.