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A population-based study of immunohistochemical detection of p53 alteration in bladder cancer

The molecular pathology of bladder cancer has been the subject of considerable interest and mutation of the p53 gene, which has been associated with more invasive bladder cancer, has been widely studied. Further, there is evidence that p53 inactivation (either mutation or protein dysregulation), ind...

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Autores principales: Kelsey, K T, Hirao, T, Schned, A, Hirao, S, Devi-Ashok, T, Nelson, H H, Andrew, A, Karagas, M R
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409723/
https://www.ncbi.nlm.nih.gov/pubmed/15083187
http://dx.doi.org/10.1038/sj.bjc.6601748
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author Kelsey, K T
Hirao, T
Schned, A
Hirao, S
Devi-Ashok, T
Nelson, H H
Andrew, A
Karagas, M R
author_facet Kelsey, K T
Hirao, T
Schned, A
Hirao, S
Devi-Ashok, T
Nelson, H H
Andrew, A
Karagas, M R
author_sort Kelsey, K T
collection PubMed
description The molecular pathology of bladder cancer has been the subject of considerable interest and mutation of the p53 gene, which has been associated with more invasive bladder cancer, has been widely studied. Further, there is evidence that p53 inactivation (either mutation or protein dysregulation), independent of stage, may be predictive of bladder cancer progression. In an effort to avoid possible biases associated with selection of more advanced cases, we examined p53 inactivation in a population-based study of bladder cancer in New Hampshire, using both mutation and immunohistochemical methods. We found the overall prevalence of mutation to be approximately 10%, while immunohistochemical analysis suggests that approximately 66% of the tumours have dysregulated p53 at the protein level. There was a significant association of mutation with persistent p53 staining, but there remained a marked number of tumours discordant for mutation and aberrant p53 immunohistochemistry. Based upon immunohistochemical staining alone, intensity rather than extent of p53 staining was more strongly related to tumour invasiveness. Additionally, all tumours with a mutation in exon 8 stained intensely. Taken together, this suggests that intense staining represents a distinct phenotype of dysfunctional protein. Our data indicate that population-based approaches to somatic alteration of p53 in bladder cancer are crucial to understanding the relationship of p53 changes to aetiology and the outcome of this disease, and further suggest that the pattern of immunohistochemical staining may represent distinct, discernible phenotypes.
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spelling pubmed-24097232009-09-10 A population-based study of immunohistochemical detection of p53 alteration in bladder cancer Kelsey, K T Hirao, T Schned, A Hirao, S Devi-Ashok, T Nelson, H H Andrew, A Karagas, M R Br J Cancer Molecular and Cellular Pathology The molecular pathology of bladder cancer has been the subject of considerable interest and mutation of the p53 gene, which has been associated with more invasive bladder cancer, has been widely studied. Further, there is evidence that p53 inactivation (either mutation or protein dysregulation), independent of stage, may be predictive of bladder cancer progression. In an effort to avoid possible biases associated with selection of more advanced cases, we examined p53 inactivation in a population-based study of bladder cancer in New Hampshire, using both mutation and immunohistochemical methods. We found the overall prevalence of mutation to be approximately 10%, while immunohistochemical analysis suggests that approximately 66% of the tumours have dysregulated p53 at the protein level. There was a significant association of mutation with persistent p53 staining, but there remained a marked number of tumours discordant for mutation and aberrant p53 immunohistochemistry. Based upon immunohistochemical staining alone, intensity rather than extent of p53 staining was more strongly related to tumour invasiveness. Additionally, all tumours with a mutation in exon 8 stained intensely. Taken together, this suggests that intense staining represents a distinct phenotype of dysfunctional protein. Our data indicate that population-based approaches to somatic alteration of p53 in bladder cancer are crucial to understanding the relationship of p53 changes to aetiology and the outcome of this disease, and further suggest that the pattern of immunohistochemical staining may represent distinct, discernible phenotypes. Nature Publishing Group 2004-04-19 2004-04-06 /pmc/articles/PMC2409723/ /pubmed/15083187 http://dx.doi.org/10.1038/sj.bjc.6601748 Text en Copyright © 2004 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This 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 license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license 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 license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular and Cellular Pathology
Kelsey, K T
Hirao, T
Schned, A
Hirao, S
Devi-Ashok, T
Nelson, H H
Andrew, A
Karagas, M R
A population-based study of immunohistochemical detection of p53 alteration in bladder cancer
title A population-based study of immunohistochemical detection of p53 alteration in bladder cancer
title_full A population-based study of immunohistochemical detection of p53 alteration in bladder cancer
title_fullStr A population-based study of immunohistochemical detection of p53 alteration in bladder cancer
title_full_unstemmed A population-based study of immunohistochemical detection of p53 alteration in bladder cancer
title_short A population-based study of immunohistochemical detection of p53 alteration in bladder cancer
title_sort population-based study of immunohistochemical detection of p53 alteration in bladder cancer
topic Molecular and Cellular Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409723/
https://www.ncbi.nlm.nih.gov/pubmed/15083187
http://dx.doi.org/10.1038/sj.bjc.6601748
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