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Blood, 1 January 2004, Vol. 103, No. 1, pp. 188-193.
Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-05-1487.
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NEOPLASIA
Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin disease
Teresa Marafioti,
Michela Pozzobon,
Martin-Leo Hansmann,
Georges Delsol,
Stefano A. Pileri, and
David Y. Mason
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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