From the Nuffield Department of Clinical Laboratory Sciences and Leukaemia Research Fund Immunodiagnostics Unit, John Radcliffe Hospital, Oxford, United Kingdom; Senckenbergisches Institut für Pathologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany; Centre de Physiopathologie de Toulouse Institut National de la Santé et de la Recherche Médicale (INSERM) (U 563), Purpan, Toulouse, France; and Cattedra di Anatomia Patologica, Servizio di Ematopatologia, Istituto di Ematologia ed Oncologia Medica "L. e A. Seragnoli," Policlinico S. Orsola, Bologna, Italy.
The neoplastic cells in classical Hodgkin disease (Reed-Sternberg cells) are of B-lymphoid origin, but they lack many markers of this cell lineage, for example, immunoglobulin, CD20, and B-cell–associated transcription factors. In contrast, the neoplastic cells ("L&H" cells) in lymphocyte predominance Hodgkin disease retain the molecular profile of germinal center B cells. In this paper, we investigated the expression in Hodgkin disease (45 cases and 3 cell lines) of 5 intracellular signaling molecules found in B cells. The Src family kinase Syk, the B-cell adaptor protein BLNK, and phospholipase C (PLC)–
2 were consistently absent from Reed-Sternberg cells, whereas 2 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 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 2 major subtypes of Hodgkin disease may be of diagnostic value.
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