EXPRESSION OF MAGE GENES IN OCULAR MELANOMA DURING PROGRESSION FROM PRIMARY TO METASTATIC DISEASE

Primary melanomas that form within the eye have a unique pattern of di sease progression as compared with melanomas that form within the skin , A high percentage of patients (approximately 50%) develop metastatic tumors that occur predominately in the liver, An unusual characterist ic of ocular melanomas is the prolonged disease-free interval that ext ends for many years between the development of primary and metastatic tumors, It is estimated that the shortest interval between disseminati on of tumor cells from the eye and the appearance of clinically detect able metastases is 6 years, A recent report indicated that fresh uveal melanoma tissue and metastatic tumor biopsies failed to express melan oma antigen gene (MAGE)-1, MAGE-2, or MAGE-3, In the present study, we examined the expression of MAGE genes on fresh and cultured tumor cel ls obtained from an ocular melanoma patient during different stages of progressive disease, MAGE gene expression was determined by reverse t ranscription-polymerase chain reaction using MAGE-1, MAGE-2 and MAGE-3 specific primers, Our results demonstrate that primary ocular tumor t issue and cultured tumor cells both express significant levels of MAGE -1, 2, and 3 at the time of enucleation, A high percentage of tumor ce lls within the primary tumor appear to express MAGE as demonstrated by consistent MAGE expression in 16 tumor cell clones, Metastatic liver tumors that developed 3 years after enucleation and 18 years after the initial formation of the primary tumor also expressed high levels of MAGE-1, -2, and -3, MAGE was expressed on fresh tumor tissue from a si ngle biopsy and cultured tumor cells obtained from three of four diffe rent metastatic tumor nodules, When the MAGE-negative metastatic tumor cells were treated with the demethylating agent 5-Aza-2-Deoxycytidine (5-Aza-dC), transcription of MAGE-1 was restored, indicating the MAGE genes were not deleted, Our results demonstrate that in some patients , MAGE genes are expressed on primary and metastatic ocular melanomas.