Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease

被引:91
作者
Falini, B
Bigerna, B
Pasqualucci, L
Fizzotti, M
Martelli, MF
Pileri, S
Pinto, A
Carbone, A
Venturi, S
Pacini, R
Cattoretti, G
Pescarmona, E
LoCoco, F
Pelicci, PG
Anagnastopoulos, I
DallaFavera, R
Flenghi, L
机构
[1] UNIV PERUGIA,INST HEMATOL,I-06100 PERUGIA,ITALY
[2] UNIV PERUGIA,INST INTERNAL MED,I-06100 PERUGIA,ITALY
[3] UNIV BOLOGNA,INST HEMATOL,BOLOGNA,ITALY
[4] CTR RIFERIMENTO ONCOL,DIV PATHOL,LEUKEMIA UNIT,I-33081 AVIANO,ITALY
[5] COLUMBIA UNIV,DEPT PATHOL,NEW YORK,NY
[6] UNIV ROMA LA SAPIENZA,INST PATHOL,ROME,ITALY
[7] UNIV ROMA LA SAPIENZA,INST HEMATOL,ROME,ITALY
[8] FREE UNIV BERLIN,INST PATHOL,W-1000 BERLIN,GERMANY
关键词
D O I
10.1182/blood.V87.2.465.bloodjournal872465
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 de-regulated 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 resetting 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. (C) 1996 by The American Society of Hematology.
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页码:465 / 471
页数:7
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