The expression of Met/hepatocyte growth factor receptor gene in giant cell tumors of bone and other benign musculoskeletal tumors.

Overexpression of the hepatocyte growth factor receptor (Met/HGF receptor), a transmembrane tyrosine kinase encoded by the MET proto-oncogene, is involved in transformation and invasive behavior of human carcinomas and sarcomas. We have previously found that bone sarcomas express high levels of Met/HGF receptor while in some cases the ligand HGF is co-expressed with the receptor, activating an autocrine loop. In this study, we analyzed 40 biopsy samples of a collection of giant cell tumors and other rare benign tumors of bone for expression of the MET proto-oncogene. These included nonossifying fibromas, osteoblastomas, desmoplastic fibromas of bone, chondroblastomas, and giant cell tumors of bone. Snap frozen samples were tested for the MET and HGF gene expression by immuno-histochemistry and Western blotting with anti-MET antibodies and RT-PCR. Over 50% of all cases scored positive for MET expression being constantly positive in recurrent or locally aggressive lesions. Sporadic co-expression of the Met/HGF receptor and ligand is also demonstrated. Met/HGF receptor expression in benign bone neoplasms suggests its early involvement in sarcomagenesis.