Expression of the c-met Gene in Invasive Ductal Carcinomas / 한국유방암학회지

PURPOSE: The c-met protein, known as the hepatocyte growth factor (HGF) receptor, is a transmembrane 190 kDa heterodimer having tyrosine kinase activity, and it is encoded by the c-met oncogene. The HGF/c-met signaling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities. Although HGF and c-met are known to be expressed in a variety of organs and they play important roles in signal transduction, studies on its expression and its correlation to the clinicopathological parameters of breast cancer are very rare. METHODS: In this study, we examined the c-met mRNA and the c-met protein expression by utilizing RT-PCR and immunohistochemical methods for 50 cases of invasive ductal carcinomas (IDCs) and 20 cases of normal breast tissues. RESULTS: The c-met mRNA amplification was detected in 35 cases of IDCs (70%), but not in the normal tissues. The c-met protein overexpression was detected in 27 cases of IDCs (54%) and 2 cases of normal breast tissue (10%). Both the mRNA amplification and protein overexpression rates were significantly higher in tumor than in the normal breast tissue. The c-met mRNA amplification showed a tendency to increase in an invasive cancer and nodal metastasis. The c-met protein overexpression was significantly correlated with the well differentiated grade of tumor and it showed a tendency to decrease in the metastatic tumors. The concordance between both the mRNA amplification and protein expressions were not observed. CONCLUSION: These results suggest that the HGF/c-met signal pathway may be associated with the development of breast cancer. c-met mRNA amplification may play important roles both in tumor progression and metastasis. c-met protein overexpression may contribute to the morphogenesis of well-differentiated tumor.

The Expression of c-met Oncogene in Thyroid Tumor / 대한내분비학회지

BACKGROUND: The proto-oncogene c-met encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), which is a pleiotropic cytokine that controls growth, survival, motility, invasive migration, and differentiation of epithelial cells. Like several other epithelial neoplasms, thyroid carcinomas have been found to overexpress the c-met oncogene. We presently examine the expression of c-met protein in thyroid tumors and the correlation of c-met protein expression with prognostic factors in thyroid cancers. METHOD: We have examined the expression of the c-met oncogene in 62 paraffin-embedded thyroid cancer specimens (54 papillary carcinomas, 5 follicular carcinomas, 2 medullary carcinomas, and 1 anaplastic carcinoma), 20 benign tumors and 20 normal tissues using immunohistochemistry. We measured both the proportion and the intensity of stained cells and then calculated the staining index by multiplying the proportion and intensity scores. The staining index were categorized to be negative/low (staining index 5). The most important prognostic factors were age (over 45), tumor size (over 1.5 cm), lymph node metastasis, capsular invasion, vascular invasion and peripheral metastasis. RESULT: 1) The rate of expression of the c-met oncogene were 100%, 100% and 60% in thyroid cancer, benign tumors and normal thyroid tissue respectively. The expression of the c-met oncogene was restricted to the membrane. 2) The staining index of normal tissue, benign tumors and thyroid carcinomas was 1.8, 4.3 and 5.8 respectively. In malignancies, the staining index of papillary carcinoma was 5.7, follicular carcinoma 5.4, medullary carcinoma 7.5, and anaplastic cancer 9. 3) A high expression of c-met was not correlated with prognostic factors in papillary, follicular carcinomas or medullay carcinomas. CONCLUSION: The c-met oncogene might not play a role in the pathogenesis of thyroid neoplasia. There was no correlation between the high expression rate of the c-met oncogene and prognostic factors in papillary and follicular carcinomas.