Heterogeneous expression of GAGE, NY-ESO-1, MAGE-A and SSX proteins in esophageal cancer: Implications for immunotherapy

Cancer/testis antigens (CTAs) elicit immune response in cancer patients and are therefore targets of immunotherapy. Current information on CTA expression is primarily based on mRNA assays and little is known about their expression at the protein level. The objectives of our study are to analyze GAGE, NY-ESO-1, MAGE-A and SSX protein expression in esophageal cancer and to correlate their expression patterns with clinicopathologic parameters and survival. We examined CTA protein expression in 213 patients with esophageal cancer by immunohistochemistry. Antigen-positive tumors were evaluated once and antigen-negative tumors were evaluated 3 times by examining different parts of the cancer specimen. GAGE, NY-ESO-1 and MAGE-A were heterogeneously expressed in 42 (20%), 44 (21%) and 111 (52%) tumors, respectively, whereas SSX expression was not detected. Of the 126 (59%) patients expressing CTAs, 70 (33%) expressed 1, 41 (19%) expressed 2 and 15 (7%) expressed 3 antigens. The expression of MAGE-A was correlated with those of GAGE (p=0.001) and NY-ESO-1 (p=0.002), and the expression of GAGE was correlated with that of NY-ESO-1 (p=0.002). One hundred fifty-six (79%) sections were positively stained in the first evaluation, whereas 37 (19%) and 4 (2%) positive sections were identified in the second and third evaluations, respectively. Particularly, MAGE and GAGE expression showed overlaps. GAGE, NY-ESO-1 and MAGE-A protein expression was not correlated with the disease progression, TNM factors or survival. The detection of immunonegative cells in every specimen suggests addition of other drugs such as 5-aza-2′-deoxycytidine to increase the therapeutic effect of CTA-specific cancer vaccines.