p21-WAF1 (wild-type p53-activated fragment 1) is involved in the control of mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases (Cdk). Because the product of WAF1 gene is a potent downstream effector of the p53 tumor-suppressor gene function, its pattern of cellular expression might correlate with nuclear accumulation of p53-encoded protein and/or p53 gone mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21-WAF1 proteins in tissue involved by non-Hodgkin's lymphomas (NHLs; 253 cases) of various histologic types. In a proportion of them (80 cases), we also investigated the possible presence of p53 gene mutations using single-strand conformation polymorphism analysis and direct DNA sequencing. The absence of both p21-WAF1 and p53 proteins was observed in 147 of 217 cases (67.7%) among CD30- NHL and in only 8 of 36 (22.2%) CD30+ cases, which were mostly anaplastic large-cell lymphomas. A consistent number ( gt 10%) of p21-WAF-expressing cells was shown in 48 of 253 (18.9%) NHL cases, with a higher incidence in CD30+ cases (25/36 (69.4%)), which mostly (21/36) coexpressed p53. These latter cases were characterized by a germline configuration of the p53 gene. In 50 of 253 NHL samples (19.7%), 47 of which (21.6%) belong to the CD30- group, neoplastic cells were p53+/p21-. In all of these cases, the p53+ cells accounted for more than 50% of neoplastic cells, up to 100%. Point mutations of p53 gene were solely observed in all investigated cases with this latter phenotype. Our findings strongly suggest that the combined immunohistochemical evaluation of p53 and p21-WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitoring and prognostication of individual cases.

P21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: A potential marker of p53 tumor-suppressor gene function

CHILOSI, Marco;KRAMPERA, Mauro;MENESTRINA, Fabio;PIZZOLO, Giovanni;SCARPA, Aldo
1996-01-01

Abstract

p21-WAF1 (wild-type p53-activated fragment 1) is involved in the control of mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases (Cdk). Because the product of WAF1 gene is a potent downstream effector of the p53 tumor-suppressor gene function, its pattern of cellular expression might correlate with nuclear accumulation of p53-encoded protein and/or p53 gone mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21-WAF1 proteins in tissue involved by non-Hodgkin's lymphomas (NHLs; 253 cases) of various histologic types. In a proportion of them (80 cases), we also investigated the possible presence of p53 gene mutations using single-strand conformation polymorphism analysis and direct DNA sequencing. The absence of both p21-WAF1 and p53 proteins was observed in 147 of 217 cases (67.7%) among CD30- NHL and in only 8 of 36 (22.2%) CD30+ cases, which were mostly anaplastic large-cell lymphomas. A consistent number ( gt 10%) of p21-WAF-expressing cells was shown in 48 of 253 (18.9%) NHL cases, with a higher incidence in CD30+ cases (25/36 (69.4%)), which mostly (21/36) coexpressed p53. These latter cases were characterized by a germline configuration of the p53 gene. In 50 of 253 NHL samples (19.7%), 47 of which (21.6%) belong to the CD30- group, neoplastic cells were p53+/p21-. In all of these cases, the p53+ cells accounted for more than 50% of neoplastic cells, up to 100%. Point mutations of p53 gene were solely observed in all investigated cases with this latter phenotype. Our findings strongly suggest that the combined immunohistochemical evaluation of p53 and p21-WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitoring and prognostication of individual cases.
1996
non-Hodgkin's lymphoma; p53; p21WAF1/CIP1
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/302978
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