BACKGROUND: Our study aims to analyze the expression pattern, mechanism, and prognostic significance of melanoma-associated antigen MAGE-C1 and MAGE-C2 in breast cancer. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to investigate the expressions of MAGE-C1 and MAGE-C2 in breast benign disease specimens, tumor-free breast specimens, and breast cancer specimens; their correlation with clinicopathologic parameters and recurrence-free survival was elucidated. We examined the influence of DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) together with histone deacetylase inhibitor trichostatin A on the expression of MAGE-C1 and MAGE-C2 in breast cancer cell lines. RESULT: Proteins for MAGE-C1 and MAGE-C2 expressions were 38.3% and 58.3% in breast cancer specimens, messenger RNA for MAGE-C1 and MAGE-C2 expressions were 43.3% and 61.7%, respectively. MAGE-C1 and MAGE-C2 expressions were positively associated with high tumor grade and reduced recurrence-free survival; MAGE-C2 expression was also associated with tumor embolus and histologic type. 5-aza-CdR treatment alone could induce expression of MAGE-C2, whereas trichostatin A was able to synergistically enhance 5-aza-CdR-mediated MAGE-C2 transcription. CONCLUSIONS: MAGE-C1 and MAGE-C2 maybe potential targets for tumor immunotherapy, and their expressions are associated with advanced breast cancer and poor outcome. (C) 2016 Elsevier Inc. All rights reserved.