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Reed-Sternberg cells of classical Hodgkin's disease react with the plasma
cell-specific monoclonal antibody B-B4 and express human syndecan-1
A Carbone, A Gloghini, V Gattei, M Degan, S Improta, D Aldinucci, V Canzonieri, T Perin, R Volpe, G Gaidano, V Zagonel and A Pinto
Division of Pathology, Centro di Riferimento Oncologico, Istituto Nazionale
di Ricovero e Cura a Carattere Scientifico, Aviano, Italy.
Although the cellular origin of Reed-Sternberg (RS) cells of classical
Hodgkin's disease (HD) has been a controversial issue for many years,
recent immunophenotypic and molecular studies have suggested that RS cells
of a subset of classical HD cases may be related to B cells. To further
define the immunophenotypic features and the differentiation stage of RS
cells, a series of 56 HD samples, including both nodular lymphocyte
predominance (LP) (eight cases) and classical HD (nodular sclerosis [NS],
32 cases; mixed cellularity [MC], 16 cases) with a non- T-cell phenotype,
were evaluated for the immunohistochemical expression of the B-B4 antigen,
a specific marker for terminally differentiated B cells. Because the cDNA
of the B-B4 antigen encodes syndecan-1, a member of a family of
transmembrane heparan sulfate proteoglycans thought to be involved in
binding cells of the B lineage to the interstitial matrix, the B-B4
immunoreactivity was correlated with the expression of syndecan-1 in
HD-derived cell lines (L428, KM-H2), as detected by both reverse
transcriptase polymerase chain reaction (RT- PCR) studies and Western
blotting. Our results show that B-B4 reacts with RS cells and their
morphological variants of all cases of classical HD, irrespective of their
antigenic phenotype (B, undetermined), albeit at a varying degree of
cellular expression. Notably, a high reactivity and staining intensity for
the B-B4 monoclonal antibody (MoAb) was restricted to tumor cells from NS
HD. In cases of the latter subtype, B-B4 positivity was also found in
sclerosis-trapped spindle cells (fibrocytes/fibroblasts). Conversely, the
putative tumor cells of nodular LP HD were consistently unreactive with the
B-B4 MoAb. Finally, we have demonstrated by RT-PCR, flow cytometry, and
Western blotting that cultured RS cells, of B and undetermined phenotype,
express syndecan-1 mRNA and produce a form of syndecan-1, recognized by the
B-B4 MoAb, which is predominantly associated with glycosaminoglycans and is
present at the cell surface. Our detection of the plasma cell-specific
antigen B-B4 (syndecan-1) on tumor cells of classical HD further supports
that RS cell progenitors may be related to germinal/postgerminal center
mature B cells and suggests that expression of syndecan-1 may contribute to
some of the typical biologic and histopathologic features of classical HD,
with a special regard to the NS subtype.
Volume 89,
Issue 10,
pp. 3787-3794,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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