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Immunolocalization of the ICE/Ced-3-family protease, CPP32 (Caspase-3), in
non-Hodgkin's lymphomas, chronic lymphocytic leukemias, and reactive lymph
nodes
S Krajewski, RD Gascoyne, JM Zapata, M Krajewska, S Kitada, M Chhanabhai, D Horsman, K Berean, LD Piro, I Fugier-Vivier, YJ Liu, HG Wang and JC Reed
The Burnham Institute, Cancer Research Center, La Jolla, CA 92037, USA.
Immunohistochemical analysis of the apoptosis-effector protease CPP32
(Caspase-3) in normal lymph nodes, tonsils, and nodes affected with
reactive hyperplasia (n = 22) showed strong immunoreactivity in the
apoptosis-prone germinal center B-lymphocytes of secondary follicles, but
little or no reactivity in the surrounding long-lived mantle zone
lymphocytes. Immunoblot analysis of fluorescence-activated cell sorted
germinal 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 lymphocytes were
replaced by CPP32-negative tumor cells. In contrast, the large cell
component of follicular mixed cells (FMs) and follicular large cell
lymphomas (FLCLs) was strongly CPP32 immunopositive in 12 of 17 (71%) and
in 8 of 14 (57%) cases, respectively, whereas the residual small-cleaved
cells were poorly stained for CPP32 in all FLCLs and in 12 of 17 (71%) FMs,
suggesting that an upregulation of CPP32 immunoreactivity 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). Immunopositivity for CPP32 was also found in
the majority of other types of non-Hodgkin'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-cell chronic lymphocyte leukemia
specimens examined were CPP32 immunopositive, whereas 3 of 3 small
lymphocytic lymphomas were CPP32 negative, suggesting that CPP32 expression
may vary depending on the tissue compartment in which these neoplastic B
cells reside. The results show dynamic regulation of CPP32 expression in
normal and malignant lymphocytes.
Volume 89,
Issue 10,
pp. 3817-3825,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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