Overexpression of c-Met protein in human thyroid tumors correlated with lymph node metastasis and clinicopathologic stage

To examine the expression of c-Met protein in thyroid tumors and the correl ation of c-Met protein expression with lymph node metastasis (LNM) and path ological stage, 111 papillary thyroid carcinomas (PTC), including 44 with s ynchronous LNM, and 117 follicular adenomas (FA) were immunohistochemically examined using dewaxed sections of formalin-fixed, paraffin-embedded tissu es. Immunohistochemical results were confirmed by Western blot analysis. Fo r PTC, positive immunostaining was observed in 107 of 111 (96.4%) cases and was diffusely present in either cytoplasm and nucleus, or only cytoplasm o r only nucleus of cancer cells at varying intensities. Staining tended to b e stronger in the periphery of cancer cell nests. Positive reaction was als o found in 44 of 117 (37.6%) cases of FA. However, the extent and intensity of c-Met immunostaining in FA were far less than those in PTC (p < 0.0001) . Forty-four PTC cases (39.6%) exhibited LNM, and the extent and intensity of c-Met expression were significantly correlated with both LNM (p < 0.0001 ) and pathological stage (p < 0.0001). No significant correlation of c-Met expression with age, sex or tumor size was found. Our findings suggest that PTC expresses c-Met protein much more strongly and intensively than does F A, and that strong and intense overexpression of c-Met protein may be an in dicator of the presence of lymph node metastasis and advanced pathological stage of papillary thyroid carcinoma.