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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-09-0002v1 16/2/455    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cheng, S. Articles by Asa, S. L Search for Related Content PubMed PubMed Citation Articles by Cheng, S. Articles by Asa, S. L

S Cheng, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada
W Liu, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada
M Mercado,
S Ezzat, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada
S Asa, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada

Correspondence: Sylvia L Asa, Email: sylvia.asa{at}uhn.on.ca

Abstract

Thyroid cancer exhibits a spectrum from relatively indolent tumors to tumors that are invasive, metastatic or progress to poorly differentiated carcinoma. Microarray expression analysis of thyroid cancer cell lines has implicated a member of the Melanoma Associated (MAGE) family of cancer-testis antigens in thyroid cancer development and progression. We performed this study to validate the role of MAGE in human thyroid cancers. A tissue microarray (TMA) of samples from 375 patients with thyroid cancer was analyzed with immunohistochemistry (IHC) to localize MAGE. Western blotting of fractionated proteins from MAGE-transfected cells was used to confirm intracellular localization of proteins. Automated analysis of TMA samples was evaluated and subjected to statistical analysis. MAGE immunoreactivity was identified in nuclear and cytoplasmic compartments of normal and malignant tissues. Specificity of staining was proved by fractionation studies that confirmed MAGE expression in nucleus and cytoplasm. Normal thyroid tissue exhibited weak cytoplasmic and strong nuclear MAGE reactivity. Tumors exhibited an increase in cytoplasmic MAGE scores that correlated with clinical behavior: larger tumors had higher MAGE scores, and there was a positive and significant correlation between MAGE cytoplasmic score and the number of histologically-proven lymph node metastases. There was a statistically significant negative correlation between cytoplasmic MAGE and the percentage of p53 positive nuclei. Our data confirm gene profiling evidence that members of the MAGE family play a role in thyroid cancer progression. The use of TMA analyses identifies IHC techniques that are translatable to the clinical setting for prognostic assessment of patients with thyroid cancer.