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

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.

Relationship between Expressions of Tumor - Associated Antigen MAGE-3 and p53 Proteins during Cell Cycle by Bivariate Analysis of Flow Cytometry / 대한암학회지

PURPOSE: MAGE (melanoma antigen gene) is a tumor associated antigen, presented by HLA class I molecules, which is recognized by cytotoxic T lymphocytes. The expression of MAGE proteins are confined to malignant tumor tissues, except for the normal testis and placental tissues. Therefore, MAGE may be a potential target for immunotherapy of malignant tumors. However, biological aspects associated with the cell cycle are not yet described. MATERIALS AND METHODS: The material used for this study was a novel human squamous cell carcinoma cell line (PNUH-12) from the hypopharynx, which had one point mutation of 78th base, C to G, in exon 7 of p53 gene. To understand the role of MAGE in relation to cell cycle and its relationship with p53 as the Gl checkpoint regulator, the expressions of MAGE-3 protein and mvtant p53 (Mtp53) were accessed by flow cytometry and immunohistochemistry. Double stains for MAGE-3/Mtp53 was analyzed with bivariate flow cytometry. DNA histograms using MAGE-3/PI (DNA) and Mtp53/PI (DNA) were also analyzed. RESULTS: The expression rate of MAGE-3 and Mtp53 were 83% and 85%, respectively. MAGE-3 was expressed in cytoplasm, while M:p53 were expressed in the nuclei of the tumor cells on the immunohistochemical sections. With bivariate analyses, coexpression rate of MAGE-3/Mtp53 was 0.96, and MAGE-3 and Mtp53 constantly showed high levels throughout the cell cycle except Go. CONCLUSIONS: These results mean that (I) MAGE-3 might have yet unknown relationship with mutant p53, (2) expressions of MAGE-3 and Mtp53 are not dependent on the cell cycle in PNUH-12 hypopharyngeal squamous carcinoma cell line, and suggest that MAGE-3 might have a role as important as p53 during the development of malignant tumors.

Paraganglioma of the Cauda Equina

Paraganglioma of the cauda equina or filum terminale is rare tumor and was first described in 1970. The authors present a case of paraganglioma of the cauda equina in a 55 year-old-man with nonspecific back pain. To our knowledge, there has been only a few report of MRI of a paraganglioma of the cauda equina. Diagnosis can be made with immunohistochemical study and electron microscopy after surgical removal. Because of frequent recurrence, total excision is mandatory.