Expression of the melanoma-associated antigen is associated with progression of human thyroid cancer.
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.
Cheng
Sonia
S
Department of Pathology, University Health Network and the Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2C4.
Liu
Wei
W
Mercado
Moises
M
Ezzat
Shereen
S
Asa
Sylvia L
SL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000556:secondary; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C072013:MAGEA3 protein, human; C095203:MAGEA6 protein, human; D009363:Neoplasm Proteins