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Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-05-1487.
Submitted May 9, 2003
Accepted July 14, 2003
Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin's disease
Teresa Marafioti*, Michela Pozzobon, Martin-Leo Hansmann, Georges Delsol, Stefano A Pileri, and David Y Mason
Nuffield Deartment of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom
Leukaemia Research Fund Immunodiagnostics Unit, University of Oxford, Oxford, United Kingdom
Senckenbergisches Institut fuer Pathologie, Klinikum der Johann Wolfgang Goethe-Universitaet, Frankfurt am Main, Germany
Centre de Physiopathologie de Toulouse, INSERM, Unite 563, C.H.U. Purpan, Toulouse, France
Cattedra di Anatomia Patologica, Servizio di Ematopatologia, Policlinico S. Orsola, Bologna, Italy
* Corresponding author; email: teresa.marafioti{at}ndcls.ox.ac.uk.
The neoplastic cells in classical Hodgkin's disease (Reed-Sternberg cells) are of B-lymphoid origin but they lack many markers of this cell lineage, e.g. immunoglobulin, CD20, B-cell-associated transcription factors. In contrast, the neoplastic cells ("L&H" cells) in lymphocyte predominance Hodgkin's disease retain the molecular profile of germinal center B cells. In this paper we investigated the expression in Hodgkin's disease (45 cases and three cell lines) of five intracellular signaling molecules found in B cells. The Src family kinase Syk, the B-cell adaptor protein BLNK, and phospholipase PLC- 2 were consistently absent from Reed-Sternberg cells, whereas two other Src kinases (Lyn and Fyn) were heterogeneously expressed in a proportion of cases (12% and 42% respectively). In contrast, the tumor cells in all cases of lymphocyte predominance Hodgkin[[rad]]s disease were positive for Fyn, Syk, BLNK and PLC-2, and Lyn immunostaining was seen in a minority of biopsies. These results indicate that in Reed-Sternberg cells the defect in B-cell lineage marker expression includes a spectrum of molecules involved in intracellular signaling, a finding in keeping with recent gene expression profiling studies. Furthermore the clear difference in expression of signaling proteins between the two major subtypes of Hodgkin's disease may be of diagnostic value.
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