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.