IMMUNOHISTOCHEMICAL ANALYSIS OF INTERLEUKIN-1-BETA-CONVERTING ENZYME CED-3 FAMILY PROTEASE, CPP32/YAMA/CASPASE-3, IN HODGKINS-DISEASE/

The Caenorhabditis elegans cell death gene, Ced-3, encodes a protein h omologous to mammalian interleukin-1 beta-converting enzyme (ICE), a c ysteine protease implicated in programmed cell death (PCD), CPP32, als o known as Yama, apopain, and Caspase-3, is a member of this family, h as substrate specificities similar to Ced-3, and has been shown to hav e an active role in PCD. Evidence suggests that these proteases act do wnstream of inhibitors of PCD such as Bcl-2 and Bcl-x(L), which are fr equently expressed in Reed-Sternberg (RS) cells of Hodgkin's disease ( HD). To date there have been no studies examining the role of the ICE/ Ced-3 family of proteins, in particular CPP32, in HD. We examined 24 c ases of HD with a classical immunophenotype and 6 cases of nodular lym phocyte predominant HD (NLPHD) for the expression of CPP32 in the RS c ells and lymphohistiocytic (L&H) cells as detected by immunohistochemi stry. Twenty two of 24 cases (92%) of HD expressed the protein in the RS cells, whereas the L&H cells in all 6 cases of NLPHD lacked express ion of CPP32. These results provide further evidence that NLPHD is a p henotypically different disease distinct from classical forms of HD. T he differential expression of the cell death protein CPP32 may be an i mportant factor contributing to the apparently different clinical beha viour of NLPHD in contrast to classical HD. The lack of expression of CPP32 in NLPHD shares similarities with low-grade B-cell non-Hodgkin's lymphomas and may explain their common clinical course. Further studi es are required to elucidate the significance of CPP32 in HD. (C) 1997 by The American Society of Hematology.