Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma.

Abstract

Hepatocyte growth factor (HGF) is a heterodimeric polypeptide growth factor that has pleiotropic roles, including those of mitogen, motogen and morphogen. The HGF receptor is characterized as a c-Met proto-oncogene product (c-Met), which is a heterodimeric tyrosine kinase receptor. Hepatocyte growth factor acts as a mediator between the mesenchymal and epithelial tissues because HGF is produced by mesenchymal cells and c-Met is mainly expressed on various epithelial cells. Furthermore, the HGF/c-Met system plays an important role in embryogenesis and the regeneration of various organs. Synovial sarcoma (SS) are unique sarcoma that show epithelial differentiation, but little is known about their histogenesis. The expression of HGF and c-Met was examined by immunohistochemistry in SS specimens from 12 patients (six each of biphasic and monophasic fibrous types). Immunohistochemical coexpression of HGF and c-Met was demonstrated in the epithelial component of five biphasic SS, while only c-Met was expressed in the epithelioid nests of three monophasic fibrous SS. The spindle cell component was negative for HGF and c-Met. In SS, positivity for epithelial markers, such as cytokeratins and epithelial membrane antigen, was diffusely observed in the epithelial component and was focally observed in spindle cells, while vimentin was positive predominantly in the spindle cell component. The areas expressing HGF and c-Met corresponded to distinct epithelial structures; however, HGF and c-Met expression were not found in any other tumor cells expressing epithelial markers in the spindle cell component of SS. Considering the morphogenic effect of HGF, which has been known to be one of its most important roles, the unique immunohistochemical localization of HGF and c-Met in SS suggests that the HGF/c-Met system may be closely related to the formation of epithelial (glandular) structures in biphasic SS.