Difference in patterns of met expression in papillary thyroid carcinomas and nonneoplastic thyroid tissue

Met protein is a tyrosine kinase receptor for hepatocyte growth factor (HGF ). c-Met has morphogenic, mitogenic, and motogenic properties and is overex pressed in many solid tumors. We studied c-met mRNA and protein expression in papillary thyroid carcinomas and nonneoplastic thyroid tissue. The c-met mRNA was detected in all biopsies by reverse transcriptase-polymerase chai n reaction and by hybridization of complex cDNA probes to a c-met-specific DNA fragment in a dot blot array. Immunohistochemistry on fresh frozen biop sies showed Met protein localized along the basal cell membrane of normal t hyrocytes in 32 of 35 nonneoplastic thyroid tissue specimens, sometimes ass ociated with weak cytoplasmic reactivity but without apical cell membrane s taining. In papillary carcinomas an increased Met protein expression was se en, comprising a cytoplasmic (33 of 49) and apical cell membrane (24 of 49) immunoreactivity;, whereas only 1 of 49 biopsies showed basal cell membran e staining. A 145-kDa Met-specific band was detected by Western immunoblott ing on protein extracts From papillary carcinomas. The tight junction prote in zona occludens-l (ZO-1), studied by immunohistochemistry, was weakly exp ressed along the apical cell membrane in 10 nonneoplastic biopsies. In cont rast, increased and cytoplasmic/apical membranous ZO-1 immunostaining was s een in 11 of 15 papillary carcinomas. Nuclear ZO-1 staining was present in a few papillary carcinomas with partial dedifferentiation. The concomitant overexpression and subcellular redistribution of Met and ZO-1 proteins indi cate a change in cell polarity in papillary carcinomas compared to nonneopl astic thyroid tissue. These observations may reflect an important feature o f the tumorigenesis of papillary thyroid carcinomas, No significant associa tion was Found between semiquantitative immunohistochemical assessment of M et protein and clinical parameters in papillary carcinoma patients.