DETECTION OF MET ONCOGENE HEPATOCYTE GROWTH-FACTOR RECEPTOR IN LYMPH-NODE METASTASES FROM HEAD AND NECK SQUAMOUS-CELL CARCINOMAS

The c-MET oncogene encodes the receptor for hepatocyte growth factor/s catter factor (HGF/SF), which is known to stimulate the invasive growt h of epithelial cells cultured in vitro. The Met/HGF receptor is a het erodimeric transmembrane tyrosine kinase, which is a prototype for a n ew family of growth factor receptors. The c-MET oncogene is expressed in several types of epithelial tissue including keratinocytes and is o ver-expressed in a number of human carcinomas. Studies on various carc inoma cell lines have shown that over-expression and structural altera tion of the receptor result in it?, activation and confer tumorigenesi s. We have studied Met/HGF receptor expression in tissue specimens fro m 34 patients with head and neck squamous cell carcinomas (HNSCC) and in 17 regional lymph node metastases. Western blot analysis was employ ed, using monoclonal antibodies directed against either the intracellu lar or extracellular domain of the receptor. Each sample was compared to its normal counterpart. The receptor did not show any major structu ral alterations in HNSCC tissues, but its expression was increased fro m 2- to 50-fold in about 70% of tumors. Immunohistochemistry then show ed that the same antibodies stained only a few cells in the basal laye r of normal squamous epithelium but intensely marked tumor cells. In t he lymph node metastases of Met-positive turners, receptor expression was maintained and sometimes increased with respect to primary tumors. Immunohistochemical analysis of the metastatic lymph nodes showed tha t cells were negative in the normal lymphatic tissue and strongly stai ned in tumor cells. Over-expression of the Met/HGF receptor was found at all tumor stages but was more significant in those associated with enlarged or multiple (N2-N3) lymph node metastases. These data show th at expression of the MEt/HGF receptor may be involved in the progressi on of HNSCC towards a metastatic phenotype and may be a useful marker of head and neck tumor cell spread to regional lymph nodes.