EXPRESSION STATUS OF BCL-6 AND SYNDECAN-1 IDENTIFIES DISTINCT HISTOGENETIC SUBTYPES OF HODGKINS-DISEASE

The tumor cells in most cases of Hodgkin's disease (HD) have been rece ntly recognized to originate from the B-cell lineage, but their precis e differentiation stage is not fully clarified. Recently, we have repo rted that the histogenesis of B-cell lymphomas may be assessed by moni toring the expression pattern of BCL-6, a transcription factor express ed in germinal center (GC) B cells, and CD138/syndecan-1 (syn-1), a pr oteoglycan associated with post-GC, terminal B-cell differentiation. I n this study, we have applied these two markers to the study of HD his togenesis. We have found that in nodular lymphocyte predominance HD (N LPHD) tumor cells consistently display the BCL-6(+)/syn-1(-) phenotype , indicating their derivation from GC B cells. Conversely, classic HD (CHD) is heterogeneous because the tumor cells of a fraction of CHD di splay the BCL-6(-)/syn-1(+) phenotype of post-GC B-cells, whereas anot her fraction of CHD is constituted by a mixture of tumor cells reflect ing the GC (BCL-6(+)/syn-1(-)) or post-GC (BCL-6(-)/syn-1(+)) phenotyp es. BCL-6(-)/syn-1(+) tumor cells of CHD are mostly found surrounded b y T cells expressing CD40L, consistent with the observation that CD40 signaling downregulates BCL-6 expression. These data indicate that tum or cells of NLPHD uniformly display a GC B-cell phenotype, whereas the phenotype of tumor cells of CHD appears to be modulated by the surrou nding cellular background, particularly CD40L(+) reactive T cells. (C) 1998 by The American Society of Hematology.