p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations

BACKGROUND: TP53 is the most frequently mutated gene in the human cancer, and the awareness of its mutational status is useful in the diagnosis and treatment of cancer patients. In the present study, we investigated the association between TP53 gene mutations and p53 immunohistochemical staining (IH...

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Autores principales: Sung, You-Na, Kim, Deokhoon, Kim, Jihun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9720942/
https://www.ncbi.nlm.nih.gov/pubmed/36471402
http://dx.doi.org/10.1186/s13000-022-01273-w
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author Sung, You-Na
Kim, Deokhoon
Kim, Jihun
author_facet Sung, You-Na
Kim, Deokhoon
Kim, Jihun
author_sort Sung, You-Na
collection PubMed
description BACKGROUND: TP53 is the most frequently mutated gene in the human cancer, and the awareness of its mutational status is useful in the diagnosis and treatment of cancer patients. In the present study, we investigated the association between TP53 gene mutations and p53 immunohistochemical staining (IHC) patterns and non-genetic effect of MDM2 as a negative regulator of p53. METHODS: A total of 135 solid cancer cases with next generation sequencing data were subjected to p53 IHC and classified as overexpression, null type or usual pattern. RESULTS: TP53 mutation was observed in 104 out of 135 cases (77.0%). When the TP53 mutations were annotated into DISRUPTED (truncations, frameshifts, splice site mutations, and deep deletions) and IF-DBD (in-frame mutations in the DNA binding domain), the null type p53 IHC pattern was associated with DISRUPTED mutations (sensitivity 86.2%, specificity 97.2%) while the overexpression pattern was associated with IF-DBD mutations (sensitivity 100%, specificity 81.7%). The specificity of p53 IHC usual pattern predicting wild type TP53 was also as high as 100%. Regardless of MDM2 amplification, p53 IHC pattern showed a perfect association with TP53 mutation pattern. CONCLUSIONS: p53 IHC pattern (overexpression, null type, usual) reasonably predicted TP53 mutational status (DISRUPTED, IF-DBD), and MDM2 amplification status did not have any impact on the p53 IHC pattern. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13000-022-01273-w.
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spelling pubmed-97209422022-12-06 p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations Sung, You-Na Kim, Deokhoon Kim, Jihun Diagn Pathol Research BACKGROUND: TP53 is the most frequently mutated gene in the human cancer, and the awareness of its mutational status is useful in the diagnosis and treatment of cancer patients. In the present study, we investigated the association between TP53 gene mutations and p53 immunohistochemical staining (IHC) patterns and non-genetic effect of MDM2 as a negative regulator of p53. METHODS: A total of 135 solid cancer cases with next generation sequencing data were subjected to p53 IHC and classified as overexpression, null type or usual pattern. RESULTS: TP53 mutation was observed in 104 out of 135 cases (77.0%). When the TP53 mutations were annotated into DISRUPTED (truncations, frameshifts, splice site mutations, and deep deletions) and IF-DBD (in-frame mutations in the DNA binding domain), the null type p53 IHC pattern was associated with DISRUPTED mutations (sensitivity 86.2%, specificity 97.2%) while the overexpression pattern was associated with IF-DBD mutations (sensitivity 100%, specificity 81.7%). The specificity of p53 IHC usual pattern predicting wild type TP53 was also as high as 100%. Regardless of MDM2 amplification, p53 IHC pattern showed a perfect association with TP53 mutation pattern. CONCLUSIONS: p53 IHC pattern (overexpression, null type, usual) reasonably predicted TP53 mutational status (DISRUPTED, IF-DBD), and MDM2 amplification status did not have any impact on the p53 IHC pattern. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13000-022-01273-w. BioMed Central 2022-12-05 /pmc/articles/PMC9720942/ /pubmed/36471402 http://dx.doi.org/10.1186/s13000-022-01273-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sung, You-Na
Kim, Deokhoon
Kim, Jihun
p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations
title p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations
title_full p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations
title_fullStr p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations
title_full_unstemmed p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations
title_short p53 immunostaining pattern is a useful surrogate marker for TP53 gene mutations
title_sort p53 immunostaining pattern is a useful surrogate marker for tp53 gene mutations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9720942/
https://www.ncbi.nlm.nih.gov/pubmed/36471402
http://dx.doi.org/10.1186/s13000-022-01273-w
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