p21WAF1 (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 gene mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21WAF1 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 p21WAF1 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 (> 10%) of p21WAF1-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 p21WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitorage and prognostication of individual cases.
ARTICLES|
November 15, 1996
p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function
M Chilosi,
M Chilosi
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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C Doglioni,
C Doglioni
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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A Magalini,
A Magalini
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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G Inghirami,
G Inghirami
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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M Krampera,
M Krampera
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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G Nadali,
G Nadali
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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D Rahal,
D Rahal
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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S Pedron,
S Pedron
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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A Benedetti,
A Benedetti
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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M Scardoni,
M Scardoni
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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E Macri,
E Macri
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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M Lestani,
M Lestani
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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F Menestrina,
F Menestrina
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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G Pizzolo,
G Pizzolo
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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A Scarpa
A Scarpa
Istituto di Anatomia Patologica, Universita di Verona, Italy.
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Blood (1996) 88 (10): 4012–4020.
Citation
M Chilosi, C Doglioni, A Magalini, G Inghirami, M Krampera, G Nadali, D Rahal, S Pedron, A Benedetti, M Scardoni, E Macri, M Lestani, F Menestrina, G Pizzolo, A Scarpa; p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function. Blood 1996; 88 (10): 4012–4020. doi: https://doi.org/10.1182/blood.V88.10.4012.bloodjournal88104012
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