C-myc oncogene expression in human melanoma and its relationship with tumour antigenicity.
Melanoma produces specific tumour antigens which are capable of eliciting an immune response. However, this tumour evades the immune system, in part, by downregulation of class I HLA antigens on the cell surface, which are required for T cell recognition. It has been suggested that the oncogene c-myc may have a role in effecting this change in vitro, however, the relationship between oncoprotein level and tumour antigenicity has not been established in human tumours. This study measured c-myc oncoprotein in 94 melanoma specimens (46 primary tumours and 48 regional metastases) using flow cytometry and evaluated class I HLA expression with immunohistochemistry. C-myc expression was found in 91 tumours (96%) with higher expression in metastases than primary melanomas (P<0.005). Class I HLA expression was found to show great variation although metastases showed less antigenicity than primary tumours (P<0.01). Analysis of the relationship between these two parameters revealed a highly significant correlation in both primary (P<0.01) and metastatic disease (P<0.01), with high oncoprotein being associated with down regulation of cell surface antigens. Knowledge of the control of tumour antigenicity is likely to provide an objective platform for the development of new strategies for immunotherapy.
Grover
R
R
RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Middlesex, UK.
Ross
D A
DA
Richman
P I
PI
Robinson
B
B
Wilson
G D
GD
D000951:Antigens, Neoplasm / Q000032:analysis*; D004273:DNA, Neoplasm / Q000032:analysis*; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I / Q000502:physiology*; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D009363:Neoplasm Proteins / Q000032:analysis*
D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins