Overexpression of melanoma-associated antigen D4 as an independent prognostic factor in squamous cell carcinoma of the esophagus.

Abstract

71 Background: To pursue an urgently needed treatment target for esophageal cancer (EC), we investigated the function of the recently discovered melanoma-associated antigen (MAGE)-D4 in squamous cell EC. Methods: MAGE-D4 mRNA expression was analyzed in nine EC cell lines using quantitative reverse transcription-polymerase chain reaction (RT-PCR). In 65 surgical specimens of squamous cell EC with no prior neoadjuvant therapy, MAGE-D4 mRNA expression in EC tissues and corresponding normal tissues was analyzed and compared, and evaluated in terms of clinicopathological factors. In representative cases, MAGE-D4 protein distribution was analyzed immunohistochemically. Results: The heterogeneity of MAGE-D4 mRNA expression was confirmed in EC cell lines by quantitative RT-PCR. In surgical specimens, MAGE-D4 mRNA expression was significantly higher in EC tissues than in corresponding normal tissues (P < 0.001). Patients with the highest MAGE-D4 mRNA expression in EC tissues (top quartile, n=17) had significantly shorter overall survival than patients with low expression (2-year survival: 44% and 73%, respectively, P = 0.006). Univariate analysis identified age (≥ 65 years), lymphatic involvement and high MAGE-D4 mRNA expression as significant prognostic factors; high MAGE-D4 mRNA expression was also an independent prognostic factor in multivariable analysis (hazard ratio: 2.194; P = 0.039), and was significantly associated with Brinkman index (P = 0.008) and preoperative carcinoembryonic antigen level (P = 0.002). Immunohistochemical MAGE-D4b expression was consistent with MAGE-D4mRNA profiling. Conclusions: Our results suggest that MAGE-D4 overexpression influences tumor progression and MADE-D4 can be a prognostic marker and a potential molecular target in squamous cell EC.