Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease

The receptor for hepatocyte growth factor (HGF) is a transmembrane tyrosine kinase that is encoded by the proto-oncogene c-met Recently, c-MET was det ected in Reed-Sternberg (RS) cells from Epstein-Barr virus-positive (EBV+) Hodgkin disease (HD). The c-MET, EBER-1, and LMP-1 expression in 45 lymph n ode biopsies and 12 bone marrow biopsies obtained from patients with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individ uals and 135 HD patients in different phases of disease. In all 45 lymph no de and 12 bone marrow samples examined, RS cells expressed c-MET but not HG F(+). These results were independent of the EBV infection. Interestingly, s everal HGF+ dendritic-reticulum cells were found scattered around c-MET+ RS cells. The mean a SEM serum HGF levels in HD patients at diagnosis and at the time of relapse were 1403 +/- 91 (95% confidence interval [CI], 1221-15 85) and 1497 +/- 242 pg/mL (95% CI, 977-2017), respectively. HGF values wer e significantly higher than those of healthy individuals (665 +/- 28 pg/mL; 95% CI, 600-721; and P < .001 for both groups of patients) and of HD patie nts in remission (616 +/- 49 pg/mL; 95% CI, 517-714; and P < .001 for both groups of patients). A significant correlation was found between serum HGF levels and B symptoms at diagnosis (P = .014). In conclusion, this study in dicates that HGF and c-MET constitute an additional signaling pathway betwe en RS cells and the reactive cellular background, thereby affecting adhesio n, proliferation, and survival of RS cells. Furthermore, the serum concentr ation of HGF in HD patients may be a useful tool in monitoring the status o f (C) 2001 by The American Society of Hematology.