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Blood, 1 February 2001, Vol. 97, No. 3, pp. 744-751
NEOPLASIA
Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1
defines novel histogenetic subsets of human immunodeficiency
virus-related lymphomas
Antonino Carbone,
Annunziata Gloghini,
Luigi M. Larocca,
Daniela Capello,
Francesco Pierconti,
Vincenzo Canzonieri,
Umberto Tirelli,
Riccardo Dalla-Favera, and
Gianluca Gaidano
From the Divisions of Pathology and Medical Oncology A,
Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS,
Aviano, Italy; the Institute of Pathology, Università Cattolica
del Sacro Cuore, Rome, Italy; the Division of Internal Medicine,
Department of Medical Sciences, "Amedeo Avogadro" University of
Eastern Piedmont, Novara, Italy; and the Institute of Cancer Genetics,
Columbia University, New York, NY.
This study was aimed at defining the histogenesis of the pathologic
spectrum of lymphoma arising in the context of human immunodeficiency virus (HIV) infection. Toward this aim, 87 AIDS-related non-Hodgkin lymphomas (AIDS-NHL) and 16 Hodgkin lymphomas arising in
HIV+ patients (HIV-HL) were comparatively analyzed for the
expression pattern of several B-cell histogenetic markers, including
BCL-6 (expressed by centroblasts and centrocytes), MUM1/IRF4 (expressed by late centrocytes and post-germinal center [GC] B cells), and CD138/syn-1 (expressed by post-GC B cells). Expression of MUM1, BCL-6,
and syn-1 segregated 3 major phenotypic patterns among AIDS-NHL and
HIV-HL: (1) the
BCL-6+/MUM1 /syn-1 pattern,
selectively clustering with a large fraction of AIDS-Burkitt lymphoma
(17 of 19) and of systemic AIDS-diffuse large cell lymphoma (12 of
16); (2) the BCL-6/MUM1+/syn-1
pattern, associated with a fraction of AIDS-immunoblastic lymphoma (8 of 24); and (3) the
BCL-6/MUM1+/syn-1+ pattern,
associated with systemic and primary central nervous system
immunoblastic lymphoma (14 of 24) and with primary effusion lymphoma
(10 of 10), plasmablastic lymphoma of the oral cavity (7 of 7), and
HIV-HL (15 of 16). Analysis of nonneoplastic lymph nodes showed that
the 3 phenotypic patterns detected in AIDS-NHL and HIV-HL correspond to
distinct stages of physiologic B-cell development centroblasts
(BCL-6+/MUM1/syn-1), late
GC/early post-GC B cells
(BCL-6/MUM1+/syn-1), and
post-GC B cells
(BCL-6/MUM1+/syn-1+). Expression
of the Epstein-Barr virus-encoded latent membrane protein-1 clustered
with the BCL-6/MUM1+/syn-1+
profile throughout the clinicopathologic spectrum of AIDS-NHL and
HIV-HL. Overall, these results define novel histogenetic subsets of
AIDS-NHL and HIV-HL and may provide novel tools for refining the
diagnosis of these disorders.
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