Expression of MAGE genes in primary and metastatic cutaneous melanoma

Abstract

Human genes MAGE-1 and MAGE-3 code for antigens that are recognized on melanoma cells by autologous cytolytic T lymphocytes. These antigens may constitute useful targets for specific anti-tumor immunization of cancer patients, since genes MAGE-1 and MAGE-3 are expressed in a number of tumors of different histological types, but are not expressed in normal adult tissues other than testis. This also applies to genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3. We have analyzed the expression of these 4 MAGE genes in cutaneous melanoma. Sixteen of 100 primary tumors vs. 69 (48%) of 145 metastases from individual patients expressed MAGE-1. Similar differences in the frequency of gene expression between primary and metastatic tumor samples were observed for MAGE-2, MAGE-3, and MAGE-4. MAGE expression in primary tumors was correlated with tumor thickness: there was a significantly increased frequency in the expression of MAGE-1, -2 and -3 in tumors of greater thickness. Benign and dysplastic nevi, as well as in situ melanomas, did not express any of the 4 MAGE genes.

Cancer testis antigens expression in mesothelioma: role of DNA methylation and bioimmunotherapeutic implications

“…CTA belonging to the MAGE, GAGE and SSX gene families were highly expressed in MM cells analysed (Table 1). This pattern of CTA expression in MM is consistent with the elevated frequency of MAGE family gene expression reported in metastatic melanomas (Brasseur et al, 1995); indeed, five out of six MM cells examined expressed MAGE-1 and/or -2, and/or -3 genes (Table 1). Noteworthy, MAGE-3 was highly expressed by MM cells; this finding suggests that MAGE-3, an extensively utilised therapeutic target for cancer immunotherapy (Marchand et al, 1999;Nishiyama et al, 2001), represents a promising candidate for CTAbased immunotherapy in the majority of MM patients.…”

“…Oligonucleotide primer sequences and gene-specific PCR amplification programs utilised have been defined for MAGE-1, -2, -3, -4 (Brasseur et al, 1995), NY-ESO-1 (Jäger et al, 1998), GAGE 1-2 (Van den Eynde et al, 1995), GAGE 1-6 (Van den Eynde et al, 1995), SSX 1-5 (dos Santos et al, 2000), SSX-2 (Sahin et al, 2000), RAGE-1 (Neumann et al, 1998), tyrosinase and Melan-A/MART-1 (van Elsas et al, 1996). The integrity of each RNA and oligo-dT-synthesised cDNA sample was confirmed by the amplification of the b-actin housekeeping gene (Coral et al, 1999).…”

Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

“…47 On an mRNA level, correlation between CT antigen expression and tumor stage has been reported in several tumors such as renal cell carcinoma, 48 bladder 49 and esophageal carcinoma, 50 and melanoma. 51 This association has not been demonstrated in others: head and neck carcinoma, 52 seminoma 18 stomach, 53 or colon. 54 In our present analysis, we did not find any correlation between tumor stage and CT antigen expression, although we documented a relationship between grade and CT antigen expression, particularly for 57B and CT7-33.…”

A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening

“…In this regard, residence on the X chromosome with a single active copy probably renders these genes more highly susceptible to derepression events. The finding that some CT antigens (e.g., MAGE and BAGE) are more frequently expressed in metastatic melanomas than primary lesions (9,30) suggests that such derepression may be a later event in tumor progression.…”