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Blood, 15 February 2001, Vol. 97, No. 4, pp. 1063-1069
NEOPLASIA
Expression of the c-met proto-oncogene and its ligand,
hepatocyte growth factor, in Hodgkin disease
Luciana Teofili,
Anna Laura Di Febo,
Francesco Pierconti,
Nicola Maggiano,
Maurizio Bendandi,
Sergio Rutella,
Antonella Cingolani,
Nicola Di
Renzo,
Pellegrino Musto,
Stefano Pileri,
Giuseppe Leone, and
Luigi Maria Larocca
From the Institutes of Hematology, Infectious Diseases,
and Pathology, Università Cattolica del Sacro Cuore, Rome, Italy;
the Department of Onco-Hematology, Division of Hematology, Casa
Sollievo della Sofferenza, S. Giovanni Rotondo, Italy; and the
Institute of Hematology Seragnoli, University of Bologna, Bologna,
Italy.
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
detected 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 node biopsies and 12 bone marrow biopsies obtained from patients
with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individuals and 135 HD patients in different phases of disease.
In all 45 lymph node and 12 bone marrow samples examined, RS
cells expressed c-MET but not HGF+. These results were
independent of the EBV infection. Interestingly, several
HGF+ dendritic-reticulum cells were found scattered around
c-MET+ RS cells. The mean ± SEM serum HGF levels in HD
patients at diagnosis and at the time of relapse were 1403 ± 91
(95% confidence interval [CI], 1221-1585) and 1497 ± 242 pg/mL
(95% CI, 977-2017), respectively. HGF values were 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
patients 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 indicates
that HGF and c-MET constitute an additional signaling pathway between
RS cells and the reactive cellular background, thereby affecting
adhesion, proliferation, and survival of RS cells. Furthermore, the
serum concentration of HGF in HD patients may be a useful tool in
monitoring the status of disease.
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