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Differential Expression of BCL-6, CD138/Syndecan-1, and Epstein-Barr
Virus-Encoded Latent Membrane Protein-1 Identifies Distinct
Histogenetic Subsets of Acquired Immunodeficiency Syndrome-Related
Non-Hodgkin's Lymphomas
Antonino Carbone,
Gianluca Gaidano,
Annunziata Gloghini,
Luigi M. Larocca,
Daniela Capello,
Vincenzo Canzonieri,
Andrea Antinori,
Umberto Tirelli,
Brunangelo Falini, and
Riccardo Dalla-Favera
From the Divisions of Pathology and Medical Oncology and AIDS
Program, Centro di Riferimento Oncologico, Istituto Nazionale di
Ricovero e Cura a Carattere Scientifico, Aviano, Italy; the Division of
Internal Medicine, the Department of Medical Sciences, University of
Torino at Novara, Novara, Italy; the Institutes of Pathology and of
Infectious Diseases, Università Cattolica del Sacro Cuore, Roma,
Italy; the Institute of Hematology, University of Perugia, Perugia,
Italy; and the Division of Oncology, the Department of Pathology,
College of Physicians and Surgeons, Columbia University, New York, NY.
This study was aimed at defining the histogenesis of the pathologic
spectrum of acquired immunodeficiency syndrome-related non-Hodgkin's
lymphomas (AIDS-NHL), including AIDS-related small noncleaved cell
lymphoma (AIDS-SNCCL), AIDS-related large noncleaved cell lymphoma
(AIDS-LNCCL), AIDS-related large cell immunoblastic lymphoma
plasmacytoid (AIDS-IBLP), and AIDS-related primary effusion lymphoma
(AIDS-PEL). Forty-six cases of AIDS-NHL were investigated for the
expression pattern of BCL-6, a protein specifically expressed by
germinal center (GC) B-cells, and CD138/syndecan-1 (syn-1), a marker of
post-GC B-cell differentiation. Expression of BCL-6 and syn-1
segregated two major phenotypic patterns among AIDS-NHL: (1) the
BCL-6+/syn-1 pattern associated with
AIDS-SNCCL and AIDS-LNCCL; (2) the BCL-6/syn-1
+ pattern associated with AIDS-IBLP and AIDS-PEL. Among
systemic AIDS-NHL infected by Epstein-Barr virus (EBV), expression of
the EBV-encoded latent membrane protein-1 (LMP-1) preferentially
associated with the BCL-6/syn-1 + profile.
Analysis of nonneoplastic lymph nodes showed that the two phenotypic
patterns detected in AIDS-NHL correspond to physiologic stages of
B-cell development, ie, GC B-cells
(BCL-6+/syn-1) and preterminally
differentiated post-GC B-cells
(BCL-6/syn-1+). Thus,
BCL-6+/syn-1 AIDS-NHL reflects a GC stage
of differentiation, whereas AIDS-NHL which are
BCL-6/syn-1+, and LMP-1+
when infected by EBV, derive from B cells that have entered post-GC plasmacell differentiation. These findings are relevant for the pathogenesis and differential diagnosis of AIDS-NHL.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 747-755
© 1998 by The American Society of Hematology.
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