Expression of the c-myc and c-fos Protooncogenes in Human Thyroid Tumors

Moon, Byung In; Kim, Chul Woo; Youn, Yeo Kyu; Oh, Seung Keun

Abstract

Some proto-oncogenes in human malignancies can be primary cause of carcinogenesis and can be correlated to histologic aggressiveness or prognosis. In this study, to define the role of c-myc and c-fos protooncogenes in multistage tumorigenesis of thyroid tumor and to correlate the expression of c-myc protooncogene with the degree of histologic aggressiveness and EORTC prognostic index in patients of thyroid carcinoma, 132 fresh specimens obtained at surgery from 71 cases of thyroid tumor were analysed by slot blot hybridization for the expression of c-myc and c-fos proto-oncogene, and 42 formalin-fixed paraffin-embedded tissues were analysed by immunohistochemical staining with monoclonal c-myc antibody and monoclonal Ki-67 antibody, and in 34 paraffin-embedded malignant tissues, the degree of histologic aggressiveness was determined, and in 42 cases of thyroid cancer, EORTC prognostic index were determined. And each item was compared to c-myc mRNA expression level. The results obtained were as follows: 1. The level of c-myc mRNA was significantly higher in malignant thyroid tissues as compared to normal or benign thyroid tissues(p=0.01). 2. The level of c-fos mRNA was similar in normal, benign and well differentiated thyroid carcinoma 3. There was no difference of c-myc mRNA expression levels between central and peripheral tumor tissues. 4. C-myc expression of normal tissues originated from cancer was higher than those from benign tumor(p=0.01) 5. A high level of c-myc mRNA in differentiated thyroid cancer corresponded to a high degree of histologic aggressiveness, although there was no statistically significant correlation between two. 6. High levels of c-myc mRNA were more frequently found in thyroid carcinoma with unfavourable prognosis, although there was no statistically significant correlation between c-myc mRNA expression and EORTC prognostic index or other prognostic factors such as age, sex, tumor size, tumor extent in thyroid carcinoma. 7. C-myc mRNA expression was statistically significantly correlated to the degree of immunohistochemical staining of monoclonal c-myc antibody(p=0.01). 8. C-myc mRNA expression was statistically significantly correlated to Ki-67 cell proliferative index score(p=0.005). On the basis of results, it can be suggested that overexpression of c-myc protooncogene in thyroid carcinoma is secondary phenotype of growth signal rather than primary cause of thyroid carcinogenesis, and expression of c-fos protooncogene was similar in normal, benign and malignant tumor tissues. C-myc may be useful prognostic indicator because there was some relationship between c-myc mRNA expression and EORTC prognostic index score or histologic aggressiveness score. And because c-myc correaltes significantly to Ki-67 cell proliferative index score, c-myc expression will be important growth signal in follicular cell of thyroid and have a role of progression of thyroid carcinoma.