p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function.

Titlep21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function.
Publication TypeJournal Article
Year of Publication1996
AuthorsChilosi M, Doglioni C, Magalini A, Inghirami G, Krampera M, Nadali G, Rahal D, Pedron S, Benedetti A, Scardoni M, Macrì E, Lestani M, Menestrina F, Pizzolo G, Scarpa A
Date Published1996 Nov 15
KeywordsBiomarkers, Cell Cycle, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases, Cyclins, DNA Mutational Analysis, Genes, p53, Humans, Lymphoma, Non-Hodgkin, Neoplasm Proteins, Phenotype, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Remission Induction, Treatment Outcome, Tumor Suppressor Protein p53

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.

Alternate JournalBlood
PubMed ID8916968
Related Faculty: 
Giorgio Inghirami, M.D.

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