Expression of MUM1/IRF4 selectively clusters with primary effusion lymphoma among lymphomatous effusions: implications for disease histogenesis and pathogenesis.
Primary effusion lymphoma (PEL) is a peculiar B-cell lymphoma characterized by infection by human herpesvirus type-8/Kaposi sarcoma-associated herpesvirus (HHV-8/KSHV) and by preferential growth in the serous body cavities. Histogenetic studies have suggested that PEL originates from B cells at a late stage of differentiation. In this study, we have investigated PEL for the expression status of MUM1/IRF4 (multiple myeloma 1/interferon regulatory factor 4) protein, which is involved in physiological B-cell maturation and represents a histogenetic marker of late B-cell differentiation. Using multiple detection assays, all cases of PEL (n = 22) were found to express MUM1/IRF4 molecules. MUM1/IRF4 expression was a selective feature of PEL among lymphomas involving the serous body cavities as secondary lymphomatous effusions generally failed to express the protein. In reactive lymphoid tissues, MUM1/ IRF4 expression clustered with advanced stages of B-cell differentiation. Comparison of MUM1/IRF4 expression with that of other histogenetic markers defined two phenotypic variants of PEL, i.e. MUM1/IRF4+, CD138/syndecan-1+, B-cell antigen- (20 out of 22 cases) and MUM1/IRF4+, CD138/syndecan-1-, B-cell antigen+ (2 out of 22 cases), suggesting a certain degree of heterogeneity in the disease histogenesis. The implications of these data are threefold. First, MUM1/IRF4 expression corroborates the notion that PEL originates from post-germinal centre, preterminally differentiated B-cells. Second, MUM1/IRF4 may help in the differential diagnosis of PEL among other lymphomas involving the serous body cavities. Finally, MUM1/IRF4 may interact with HHV-8/KSHV-encoded interferon regulatory factors (IRFs) and thus contribute to PEL escape from interferon-mediated control of viral infection.
Carbone
A
A
Division of Pathology, Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, Aviano, Italy. acarbone@ets.it
Gloghini
A
A
Cozzi
M R
MR
Capello
D
D
Steffan
A
A
Monini
P
P
De Marco
L
L
Gaidano
G
G
D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors; D008198:Lymph Nodes / Q000737:chemistry; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis; D018448:Models, Immunological; D017354:Point Mutation; D011509:Proteoglycans / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D000099218:Interferon Regulatory Factor-4
D000944:Antigens, Differentiation, B-Lymphocyte; D015415:Biomarkers; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C508241:SDC1 protein, human