Granzyme B expression in Reed-Sternberg cells of Hodgkin's disease.
Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neoplastic cells in Hodgkin's disease. Although most data suggest a lymphoid origin, the nature of these cells still remains the subject of considerable controversy. Recently, monoclonal antibodies became available, directed against granzyme B, a serine protease specifically expressed by activated cytotoxic T cells (CTLs) and natural killer (NK) cells. Using two granzyme B-specific antibodies directed against different epitopes, we studied the expression of granzyme B in a well characterized group of Epstein-Barr virus (EBV)-positive and EBV-negative cases of Hodgkin's disease. Granzyme B expression was found in part of the H-RS cells in 11 out of 61 tested cases (18%, 9 of 46 cases of nodular sclerosing and 1 of 12 mixed cellularity Hodgkin's disease). In none of these cases did H-RS cells express B-cell markers, whereas in four cases, expression of either the T-cell marker CD3 or CD8 was found in a small minority of H-RS cells. The percentage of granzyme B-positive H-RS cells ranged from < 10% to > 50%. Granzyme B-positive H-RS cells were present in 6 of 26 EBV-positive cases and in 5 of 35 EBV-negative cases, indicating no relationship with the presence of EBV. Moreover, no significant differences were found regarding either stage at presentation or clinical outcome. We conclude that in a restricted number of cases of Hodgkin's disease, the H-RS cells express granzyme B, and therefore might be considered the neoplastic equivalent of either activated CTLs or NK cells.
Oudejans
J J
JJ
Department of Pathology, Free University Hospital Amsterdam, The Netherlands.
Kummer
J A
JA
Jiwa
M
M
van der Valk
P
P
Ossenkoppele
G J
GJ
Kluin
P M
PM
Kluin-Nelemans
J C
JC
Meijer
C J
CJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D002648:Child; D005260:Female; D053804:Granzymes; D006689:Hodgkin Disease / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D016539:Reed-Sternberg Cells / Q000201:enzymology* / Q000276:immunology; D012697:Serine Endopeptidases / Q000032:analysis*
D015703:Antigens, CD; D009363:Neoplasm Proteins; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases