Expression of the MAGE-1, -2, -3, -4, -5, and -10 Genes in Thyroid Cancers / 대한내분비학회지

ABSTRACT

BACKGROUND: MAGE(melanoma antigen gene) has been named as cancer/testis specific antigens since its expression is only detected in the testis or cancer cells. Because of its relatively specific expression in cancer cells, it has been considered as a marker for the early diagnosis of several cancers, or as an appropriate target for a specific immunotherapy mediated by cytotoxic T lymphocytes. Therefore, there have been many reports concerning the expression of MAGE genes in various types of malignant tumors, although only a few reports in human thyroid neoplasms. The purpose of this study was to determine whether the MAGE-1, -2, -3, -4, -5, and -10 genes expressed in different histological types of thyroid tumors and to elucidate the clinical usefulness of MAGE genes on the diagnosis of thyroid tumors. METHODS: Thirty-eight patients who had undergone thyroidectomy at Kosin Medical Center between January and August, 1999 were included in the study. Of the 38 patients enrolled, 26 exhibited papillary carcinoma, 3 papillary carcinoma with lymph node metastasis, 1 follicular carcinoma, 1 medullary carcinoma, 5 nodular hyperplasia, 1 adenomatous goiter, and 1 follicular carcinoma. In the twelve normal control thyroid tissues, total cellular mRNA was extracted from 31 cancer tissues and 7 benign tissues, RT-PCR was run in 35 cycles, with specific primers of the subtypes of MAGE genes. With probes confirmed by DNA sequencing, the isolates were reevaluated by Southern blot hybridization. RESULTS: In the 26 papillary carcinomas, MAGE-1,-2,-3,-4,-5 and -10 genes were expressed in 88.5%, 92.3%, 3.8%, 26.9%, 26.9%, and 0% by RT-PCR respectively. In the three papillary carcinomas with regional lymph node metastasis, MAGE-1, -2 and -5 genes expressed in two of the three, and MAGE-4 in one of the three cases. In the one medullary carcinoma, the MAGE-1,-2,-4, and MAGE-5 genes were expressed, and in the one case of follicular carcinoma, only the MAGE-2 gene was expressed. In contrast, none of the 7 benign tumors and 12 normal control tissues expressed any of these MAGE genes. The sensitivity of MAGE-1,-2,-3,-4,-5 and -10 genes in thyroid tumors was 83.8%, 90.3%, 3%, 29.0%, 32.3%, and 0%, respectively and the specificity was 100%. CONCLUSION: These results demonstrate that MAGE genes were expressed in the malignant thyroid tumors but not in the benign tumors and normal tissues. Among the MAGE gene families, MAGE-1 and -2 genes were more sensitive than MAGE-3, 4,-5 and -10 genes. However, in order to demonstrate if the MAGE genes could be used for the diagnosis of follicular carcinoma and distant metastasis in thyroid tumors, further study is required.