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American Journal of Pathology, Vol 148, 233-240, Copyright © 1996 by American Society for Investigative Pathology
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JJ Oudejans, JA Kummer, M Jiwa, P van der Valk, GJ Ossenkoppele, PM Kluin, JC Kluin-Nelemans and CJ Meijer
Department of Pathology, Free University Hospital Amsterdam, The Netherlands.
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.
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