Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease

Antonino Carbone, Annunziata Gloghini, Donatella Aldinucci, Valter Gattei, Riccardo Dalla-Favera, Gianluca Gaidano

Research output: Contribution to journalArticlepeer-review

Abstract

Biological and clinical studies have shown that Hodgkin's disease (HD) can be divided into two major categories, termed nodular lymphocyte predominance HD (NLP HD) and classic HD (CHD). Within CHD four subtypes have been distinguished: nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depletion. To refine the histogenesis of the pathological spectrum of HD, 75 CHD and 13 NLP HD were analysed for the expression pattern of MUM1/IRF4 (Multiple Myeloma-1/Interferon Regulatory Factor-4), a lymphocyte- specific member of the IRF family, that is expressed by late centrocytes and post-germinal centre (GC) B cells. MUM1 reacted with Hodgkin's and Reed-Sternberg (HRS) cells of all CHD cases (75/75 cases), with a moderate to strong staining intensity. Conversely, lymphocyte and histiocyte (L & H) cells, the putative tumour cells of NLP HD, were negative for MUM-1 expression (9/13 cases) or displayed a weak reactivity for the antigen in <10% neoplastic cells (4/13 cases). With respect to HD microenvironment, NLP HD displayed numerous MUM1-positive T lymphocytes located in close proximity to L & H cells whereas, in CHD, MUM1-positive T lymphocytes appeared to be distributed randomly with no specific relationship with HRS cells. Overall, this study shows that MUM1 expression differs in L & H cells versus HRS cells, corroborating the notion that NLP HD and CHD represent different stages of B-cell differentiation. As MUM1-positive T lymphocytes form rosettes around tumour cells of NLP HD, but not of CHD, these data point also to differences in the microenvironment of NLP HD and CHD, and postulate an interactive role of MUM1-positive T lymphocytes with L & H cells.

Original languageEnglish
Pages (from-to)366-372
Number of pages7
JournalBritish Journal of Haematology
Volume117
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • H cells
  • Histogenesis
  • Hodgkin's disease
  • L &
  • Microenvironment
  • MUM1/IRF4

ASJC Scopus subject areas

  • Hematology

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