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Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte
predominance Hodgkin's disease
B Falini, B Bigerna, L Pasqualucci, M Fizzotti, MF Martelli, S Pileri, A Pinto, A Carbone, S Venturi, R Pacini, G Cattoretti, E Pescarmona, F Lo Coco, PG Pelicci, I Anagnastopoulos, R Dalla-Favera and L Flenghi
Institute of Hematology, University of Perugia, Italy.
The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein
is rearranged in about 30% diffuse large B-cell lymphomas and is expressed
predominantly in normal germinal center B cells and related lymphomas.
These findings suggest that BCL-6 may play a role in regulating
differentiation of normal germinal center B cells and that its deregulated
expression caused by rearrangements may contribute to lymphomagenesis. This
prompted us to investigate the expression of the BCL-6 protein in Hodgkin's
disease (HD), focusing on the nodular lymphocyte predominance subtype
(NLPHD), which differs from classical HD by virtue of the B-cell nature of
the malignant cell population (so- called L&H cells) and its
relationship with germinal centers. Forty-one HD samples (19 NLPHD, 12
nodular sclerosis, and 10 mixed cellularity) were immunostained with the
monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive
and a formalin-resistant epitope on the aminoterminal region of the BCL-6
gene product, respectively. Strong nuclear positivity for the BCL-6 protein
was detected in tumor (L&H) cells in all cases of NLPHD. In contrast,
BCL-6 was expressed only in a small percentage of Hodgkin and
Reed-Sternberg cells in about 30% of classical HD cases. Notably, the
nuclei of reactive CD3+/CD4+ T cells nearby to and rosetting around L&H
cells in NLPHD were also strongly BCL-6+, but lacked CD40 ligand (CD40L)
expression. This staining pattern clearly differed from that of classical
HD, whose cellular background was made up of CD3+/CD4+ T cells showing the
BCL-6-/CD40L+ phenotype. These results further support the concept that
NLPHD is an histogenetically distinct, B-cell-derived subtype of HD and
suggest a role for BCL-6 in its development.
Volume 87,
Issue 2,
pp. 465-471,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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