Immunolocalization of the ICE/Ced-3-family protease, CPP32 (Caspase-3), in non-Hodgkin's 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 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.
Krajewski
S
S
The Burnham Institute, Cancer Research Center, La Jolla, CA 92037, USA.
Gascoyne
R D
RD
Zapata
J M
JM
Krajewska
M
M
Kitada
S
S
Chhanabhai
M
M
Horsman
D
D
Berean
K
K
Piro
L D
LD
Fugier-Vivier
I
I
Liu
Y J
YJ
Wang
H G
HG
Reed
J C
JC
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000473:pathology; D008198:Lymph Nodes / Q000201:enzymology*; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D014066:Palatine Tonsil / Q000166:cytology; D011817:Rabbits
D009363:Neoplasm Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases