Expression of c-met Gene in Thyroid Tumors

Cha, Hee Jeong; Cho, Seong Jin; Yoo, Chong Woo; Chang, Wu Young; Kang, Hee Joon; Joo, Sun Hyung; Park, Chan Heun; Park, Cheol Jae

Abstract

PURPOSE
The hepatocyte growth factor, (HGF)/c-Met, pathway may play various roles in the carcinogenesis of various organs. HGF, a ligand for c-Met, is a pleiotrophic factor that was originally identified as a polypeptide growth factor for hepatocytes. Met protein, known as the HGF receptor, is a transmembrane 190 kDa heterodimer with tyrosine kinase activity, which is encoded by the c-met oncogene. The HGF/ c-Met signalling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities. Although the c-met gene is known to be expressed in a variety of tissues and play important roles in signal transduction, studies of its expression in thyroid tumors are rare. Our objectives were to evaluate the c-met gene expression in benign and malignant thyroid tumors and to correlate this with various clinicopathological facors. METHODS: In this study, the mRNA expression of the c-met was examined by means of a RT-PCR method and the from immunohistochemical expression of c-Met protein in 100 cases of thyroid tumors cases, including 50 papillary carcinomas (pc), 10 follicular carcinomas (fc), and 20 follicular adenomas (fa), 20 nodular hyperplasia (nh). RESULTS: c-met mRNA expression was detected in 10, 20, 40 and 86% of the nh, fa, fc and pc, respectively. Also, c-Met protein expression was detected in 5, 15, 20 and 88% of the nh, fa, fc and pc, respectively. Especially, the c-Met protein expression was higher in well differentiated papillary carcinomas than those that were poorly differentiated, and was statistically significant. Correlation between c-met mRNA and protein expression was recognized in papillary carcinomas. CONCLUSION: These results suggest that the expression of c-met gene expression may be associated with the development of papillary carcinomas of the thyroid. Also, both c-met mRNA and protein expressions may contribute to the morphogenesis of well differentiated papillary carcinomas.