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.

The Expression of c-met, c-Ha-ras and c-myc Oncogene in Thyroid Papillary Cancer and Prognostic Factor

BACKGROUND: Many oncogenes have been recently identified in human thyroid carcinomas, but the molecular mechanisms that lead to thyroid neoplasia are not well understood. To assess whether oncogene- encoded proteins can be regarded as useful prognostic indicators, we have evaluated the expressions of c-met, c-Ha-ras, c-myc oncogenes in patients with papillary thyroid cancer (PTC) in relation to the prog nostic factors. METHODS: We used immunohistochemistry to examine the expressions of c-met, c-Ha-ras, and c-myc oncogenes in 54 paraffin-embedded PTC specimens. We measured both the proportion (scale of 0-3) and the intensity (scale of 0-3) of the stained cells and then calculated the staining index (scale of 0-9) by multiplying the proportion and the intensity scores. The staining index was thus categorized as negative/low (staining index 5). The considered prognostic factors were age (over 45), tumor size (over 1.5 cm), lymph node metastasis, capsular invasion, vascular invasion, and distant metastasis. RESULTS: 1) The rates of expression of c-met, c-Ha-ras, c-myc oncogenes were 100%, 81.5%, and 70.3% in papillary thyroid cancer and 100%, 30%, and 10% in benign tumors and 60%, 10%, and 0% in normal thyroid tissue, respectively. The expression of c-met oncogene was restricted to the membrane the expression of c-Ha-ras was stromal in 95.5% of the specimens, and that of c-myc was stromal in 94.7%. 2) High expression (staining index >5) of c-met, c-Ha-ras and c-myc were not associated with the prognostic factors such as age, tumor size, lymph node metastasis, capsular invasion, vascular invasion and distant metastasis. CONCLUSION: Although the rates of expression of c-met, c-Ha-ras, and c-myc oncogenes were high in papillary carcinomas (100%, 81.5%, and 70.3%, respectively), there was no relationship between the high expression rates of the oncogenes and prognostic factors.