EXPRESSION OF CD95 ANTIGEN AND BCL-2 PROTEIN IN NON-HODGKINS-LYMPHOMAS AND HODGKINS-DISEASE

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerv e growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 ex pression is upregulated on activated T and B lymphocytes and natural k iller cells, where binding of the antigen by anti-Pas and anti-APO-1 a ntibodies has been shown to induce apoptosis. This CD95-mediated apopt osis is at least partially inhibited by expression of the Bcl-2 protoo ncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regula tion of lymphoid neoplasms, we studied by immunohistochemistry the exp ression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 case s of Hodgkin's disease In all, 29 B and 2 T cell lymphomas, and 9 case s of Hodgkin's disease expressed CD95. Compared with diffuse large B-c en and Burkitt-like Lymphomas, low-grade B-cell lymphomas more frequen tly expressed CD95 (52% versus 26%; P < .005). None of the B-cell smal l lymphocytic lymphomas or mantle cell lymphomas expressed CD95, where as the majority of follicle center lymphomas, extranodal marginal zone B-cea lymphomas, and immunocytomas were CD95(+). Of the 29 CD95(+) B- cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, co mpared with 87% of the low-grade group CP < .04). Two of three periphe ral T-cell lymphomas-including one anaplastic large cell lymphoma-expr essed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's d isease The infrequent expression of CD95 in high-grade B-cell lymphoma s suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediate d apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the a poptosis signal delivered by CD95.