High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma.

TitleHigh levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma.
Publication TypeJournal Article
Year of Publication1993
AuthorsCesarman E, Inghirami G, Chadburn A, Knowles DM
JournalAm J Pathol
Date Published1993 Sep
KeywordsAdolescent, Adult, Aged, Antigens, Neoplasm, Base Sequence, Cloning, Molecular, DNA, Neoplasm, Female, Gene Expression, Genes, p53, Humans, Immunohistochemistry, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Molecular Sequence Data, Mutation, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Tumor Suppressor Protein p53

Strong immunohistochemical reactivity for p53 tumor suppressor gene product has been reported in a variety of different human malignancies including CD30- (Ki-1) positive anaplastic large cell lymphoma (ALCL). Although high levels of p53 protein have been interpreted as abnormal, rapidly proliferating benign and neoplastic lymphoid cells may have increased p53 expression in the absence of structural alterations. On the other hand, mutations in the p53 gene can lead to a lack of p53 protein production. Structural alterations of the p53 gene have not been documented in cases of ALCL and the mechanism for an abnormal pattern of p53 expression in these lymphomas has not been elucidated. Therefore, to determine whether an altered pattern of p53 expression correlates with mutations in the p53 locus in ALCL, we analyzed the expression of p53 protein immunohistochemically, compared it with the proliferation index using monoclonal antibody Ki-67, and assessed the presence of mutations in exons 5 though 9 of the p53 gene using a single-strand conformation polymorphism assay in a panel of 17 ALCLs. Furthermore, we studied the presence of allelic deletions of chromosome 17p by restriction fragment length polymorphism analysis. We found significant levels of p53 protein expression in 12 of the 15 cases studied, but identified mutations in only one of 17 cases. An allelic deletion in chromosome 17p was identified only in the one case containing a mutated p53 gene. Whereas the case containing structural alterations in the p53 gene did have strong p53 immunoreactivity, 11 cases that lacked p53 mutations in the regions examined also had significant levels of p53. Thus, our studies indicate that strong immunohistochemical reactivity for p53 is not a reliable indicator of the presence of structural alterations of p53 gene exons 5 through 9 in ALCL.

Alternate JournalAm J Pathol
PubMed ID8103295
PubMed Central IDPMC1887225
Grant ListCA48236 / CA / NCI NIH HHS / United States
EY06337 / EY / NEI NIH HHS / United States
Related Faculty: 
Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D. Giorgio Inghirami, M.D.

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