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| p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: A potential marker of p53 tumor-suppressor gene function |
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| Author(s): Chilosi M, Doglioni C, Magalini A, Inghirami G, Krampera M, Nadali G, Rahal D, Pedron S, Benedetti A, Scardoni M, Macri E, Lestani M, Menestrina F, Pizzolo G, Scarpa A |
| Source: BLOOD Volume: 88 Issue: 10 Pages: 4012-4020 Published: NOV 15 1996 |
| Times Cited: 61 References: 70 |
| 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 gene 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 (>10%) of p21(WAF1)-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 monitorage and prognostication of individual cases. (C) 1996 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Chilosi, M (reprint author), UNIV VERONA, POLICLIN BORGO ROMA, IST ANAT PATOL, I-37134 VERONA, ITALY |
Addresses:
1. UNIV VERONA, CATTEDRA EMATOL, I-37100 VERONA, ITALY
2. NYU, NEW YORK, NY USA
3. OSPED CIVILE BELLUNO, BELLUNO, ITALY |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 |
| Subject Category: Hematology |
| IDS Number: VU984 |
| ISSN: 0006-4971 |
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