Expression of hepatocyte growth factor (HGF) and its receptor (MET) in medullary carcinoma of the thyroid

The tyrosine kinase receptor encoded by the MET oncogene has the unusual pr operty of mediating the invasive growth of epithelial cells upon binding wi th the hepatocyte growth factor (HGF). The MET/HGF receptor is known to be overexpressed in thyroid carcinomas originated from follicular cells, but h as not been reported in C cell tumors. To investigate the role of HGF and o f its receptor (encoded by MET oncogene] in medullary carcinoma of the thyr oid (MCT), we studied the expression of HGF and MET in 20 cases by means of different techniques. By RT-PCR, HGF mRNA was found in 10/20 cases, while MET mRNA presence was demonstrated in 8/20, of which 7 also expressed HGF. Northern blot analysis and in situ hybridization were performed in selected cases and confirmed RT-PCR data in some cases, although the lower sensitiv ity of these procedures did not allow the identification of all RT-PCR posi tive cases. By immunohistochemistry (using specific monoclonal antibodies) HGF was demonstrated in 8/9 RT-PCR positive cases and a monoclonal to MET i mmunostained 5/6 RT-PCR positive cases. All receptor positive cases also ex pressed the ligand in the same tumor cell population. These findings demons trate MET and HGF co-expression in a subset of MCT, in which autocrine/para crine circuits may be active. No correlation was found between HGF/MET expr ession and clinico-pathological parameters, except for the more common mult ifocality of HGF/MET positive MCT. Whether the potential activation of MET in MCT is responsible for local invasion and malignant evolution is to be f urther investigated, especially in multifocal and aggressive tumors.