c-met expression in tall cell variant papillary carcinoma of the thyroid

BACKGROUND. Tall cell variant papillary carcinoma of the thyroid demonstrates unusually aggressive clinical behavior compared with the usual form of papillary thyroid carcinoma. The proto-oncogene c-met encodes a tyrosine kinase receptor known to influence cell invasion. This current study examined c-Met expression in tall cell variant tumors compared with other types of papillary thyroid carcinoma and benign thyroid disease. METHODS. c-Met expression in 60 archived thyroid specimens was evaluated by immunohistochemical staining. RESULTS. Tall cell variant specimens expressed significantly greater levels of c-Met than other forms of papillary thyroid carcinoma and benign thyroid disease (P < 0.0001). c-Met expression was significantly different for the following pairs of histologies: tall cell variant versus usual papillary carcinoma of the thyroid (P < 0.0001), tall cell variant versus follicular variant papillary thyroid carcinoma (P < 0.0001), tall cell variant versus benign thyroid (P < 0.0001), and usual papillary carcinoma of the thyroid versus benign thyroid (P = 0.005). In addition, for all types of papillary carcinomas evaluated, c-Met expression was significantly higher in specimens with extracapsular spread (P = 0.01) and skeletal muscle invasion (P = 0.02), and approached significance for specimens with lymphatic invasion (P = 0.06). After adjusting for extracapsular spread, c-Met expression was still found to be associated significantly with tall cell histology (P < 0.0001). CONCLUSIONS. c-Met expression is a significant marker for tall cell variant papillary carcinoma of the thyroid and its invasive behavior. This finding may explain the unusually aggressive behavior of this tumor and suggests a role for c-Met in the early identification of patients with tall cell variant thyroid disease. Cancer 2003; 98:1386-93. (C) 2003 American Cancer Society.