Tissue Microarray Evaluation of Melanoma Antigen E (MAGE) Tumor-Associated Antigen Expression: Potential Indications for Specific Immunotherapy and Prognostic Relevance in Squamous Cell Lung Carcinoma

Tumor-associated antigens (TAAs) of the Melanoma antigen E (MAGE) family were the first described in humans. 1 They belong to the so-called cancer/testis TAA subclass encoded by genes expressed in tumors of unrelated histologic origin and in a restricted number of healthy tissues. 2,3 Several epitopes derived from these TAAs and recognized by HLA class I restricted cytotoxic T cells have been identified. 1,4–6 Ongoing clinical trials suggest that specific immunization procedures could lead to clinically effective antitumor immune responses. 7,8 A small number of monoclonal antibodies (mAbs) specific for MAGE TAA gene products have been generated and used to confirm polymerase chain reaction data and to assess the extent of their expression in neoplastic cells from clinical samples. 2,9,10 Interestingly, they were also instrumental in demonstrating MAGE TAA in cancer cells such as Reed-Sternberg cells where unequivocal polymerase chain reaction data could not be generated. 11 Tissue microarray technology (TMA) takes advantage of tissue cylinders (diameter 0.6 mm) derived from hundreds of different primary tumor blocks and subsequently brought into one empty “recipient” paraffin block. Sections from such array blocks can then be used for simultaneous analysis of hundreds or thousands of tumors at the DNA, RNA, or protein level. Most importantly, specific TMA databases including relevant clinical information related to individual specimens have also been produced. Thus, TMAs offer the unique opportunity to combine large sets of pathologic and clinical data in an attempt to evaluate the potential significance of the expression of specific markers. 12 In this study we used a multitumor TMA containing 3,520 samples from 197 different tissues to comprehensively evaluate MAGE TAA expression as detectable by immunohistochemistry, taking advantage of a specific mAb. Furthermore, a non-small-cell lung cancer (NSCLC) TMA was used to address the prevalence of the expression of these TAAs and their correlation with histologic and clinical data in these tumors. We report here that the exquisite tumor specificity of MAGE TAA expression is correlated with unfavorable prognosis in NSCLC.