IMMUNOLOCALIZATION OF THE ICE CED-3-FAMILY PROTEASE, CPP32 (CASPASE-3), IN NON-HODGKINS-LYMPHOMAS, CHRONIC LYMPHOCYTIC LEUKEMIAS, AND REACTIVE LYMPH-NODES/

Immunohistochemical analysis of the apoptosis-effector protease CPP32 (Caspase-3) in normal lymph nodes, tonsils, and nodes affected with re active hyperplasia (n = 22) showed strong immunoreactivity in the apop tosis-prone germinal center B-lymphocytes of secondary follicles, but little or no reactivity in the surrounding long-lived mantle zone lymp hocytes. Immunoblot analysis of fluorescence-activated cell sorted ger minal center and mantle zone B cells supported the immunohistochemical results. In 22 of 27 (81%) follicular small cleaved cell non-Hodgkin' s B-cell lymphomas, the CPP32-immunopositive germinal center lymphocyt es were replaced by CPP32-negative tumor cells. In contrast, the large cell component of follicular mixed cells (FMs) and follicular large c ell lymphomas (FLCLs) was strongly CPP32 immunopositive in 12 of 17 (7 1%) and in 8 of 14 (57%) cases, respectively, whereas the residual sma ll-cleaved cells were poorly stained for CPP32 in all FLCLs and in 12 of 17 (71%) FMs, suggesting that an upregulation of CPP32 immunoreacti vity occurred during progression. Similarly, cytosolic immunostaining for CPP32 was present in 10 of 12 (83%) diffuse large cell lymphomas ( DLCLs) and 2 of 3 diffuse mixed B-cell lymphomas (DMs). Immunopositivi ty for CPP32 was also found in the majority of other types of non-Hodg kin's lymphomas studied. Plasmacytomas were CPP32 immunonegative in 4 of 12 (33%) cases, in contrast to normal plasma cells, which uniformly contained intense CPP32 immunoreactivity, implying downregulation of CPP32 in a subset of these malignancies. All 12 peripheral blood B-cel l chronic lymphocyte leukemia specimens examined were CPP32 immunoposi tive, whereas 3 of 3 small lymphocytic lymphomas were CPP32 negative, suggesting that CPP32 expression may vary depending on the tissue comp artment in which these neoplastic B cells reside. The results show dyn amic regulation of CPP32 expression in normal and malignant lymphocyte s. (C) 1997 by The American Society of Hematology.