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TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases
Mutations in tumor suppressor TP53 have been inconsistently linked to breast cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary clinical means of TP53 mutation determination, only detects mutations that facilitate protein accumulation (e.g., missense mutations). RNA-bas...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018637/ https://www.ncbi.nlm.nih.gov/pubmed/29951581 http://dx.doi.org/10.1038/s41523-018-0067-5 |
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author | Williams, Lindsay A. Butler, Ebonee N. Sun, Xuezheng Allott, Emma H. Cohen, Stephanie M. Fuller, Ashley M. Hoadley, Katherine A. Perou, Charles M. Geradts, Joseph Olshan, Andrew F. Troester, Melissa A. |
author_facet | Williams, Lindsay A. Butler, Ebonee N. Sun, Xuezheng Allott, Emma H. Cohen, Stephanie M. Fuller, Ashley M. Hoadley, Katherine A. Perou, Charles M. Geradts, Joseph Olshan, Andrew F. Troester, Melissa A. |
author_sort | Williams, Lindsay A. |
collection | PubMed |
description | Mutations in tumor suppressor TP53 have been inconsistently linked to breast cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary clinical means of TP53 mutation determination, only detects mutations that facilitate protein accumulation (e.g., missense mutations). RNA-based pathway methods capture functional status and may aid in understanding the role of TP53 function in racial disparities of breast cancer. TP53 status was assessed among invasive breast cancer cases from the Carolina Breast Cancer Study (CBCS) (2008–2013) using IHC and an established RNA-based TP53 signature (CBCS and The Cancer Genome Atlas (TCGA)). Frequency of TP53 status (IHC, RNA-based) was estimated in association with tumor characteristics, PAM50 intrinsic subtype, age, and race using relative frequency differences (RFDs) and 95% confidence intervals (95% CI) as the measure of association. Approximately 60% of basal-like tumors were TP53 protein positive (IHC), while nearly 100% were TP53 mutant-like (RNA). Luminal A tumors had low frequency of TP53 positivity (IHC: 7.9%) and mutant-like status (RNA: 1.7%). Mutant-like TP53 (RNA) was strongly associated with age ≤50 years, high tumor grade, advanced stage of disease, large tumor size, and basal-like and HER2 intrinsic subtypes. Black race was strongly associated with TP53 mutant-like status (RNA) (RFD: 24.8%, 95% CI: 20.5, 29.0) even after adjusting for age, grade, stage (RFD: 11.3%; 95% CI: 7.6, 15.0). Associations were attenuated and non-significant when measured by IHC. IHC-based TP53 status is an insensitive measurement of TP53 functional status. RNA-based methods suggest a role for TP53 in tumor prognostic features and racial disparities. |
format | Online Article Text |
id | pubmed-6018637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60186372018-06-27 TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases Williams, Lindsay A. Butler, Ebonee N. Sun, Xuezheng Allott, Emma H. Cohen, Stephanie M. Fuller, Ashley M. Hoadley, Katherine A. Perou, Charles M. Geradts, Joseph Olshan, Andrew F. Troester, Melissa A. NPJ Breast Cancer Article Mutations in tumor suppressor TP53 have been inconsistently linked to breast cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary clinical means of TP53 mutation determination, only detects mutations that facilitate protein accumulation (e.g., missense mutations). RNA-based pathway methods capture functional status and may aid in understanding the role of TP53 function in racial disparities of breast cancer. TP53 status was assessed among invasive breast cancer cases from the Carolina Breast Cancer Study (CBCS) (2008–2013) using IHC and an established RNA-based TP53 signature (CBCS and The Cancer Genome Atlas (TCGA)). Frequency of TP53 status (IHC, RNA-based) was estimated in association with tumor characteristics, PAM50 intrinsic subtype, age, and race using relative frequency differences (RFDs) and 95% confidence intervals (95% CI) as the measure of association. Approximately 60% of basal-like tumors were TP53 protein positive (IHC), while nearly 100% were TP53 mutant-like (RNA). Luminal A tumors had low frequency of TP53 positivity (IHC: 7.9%) and mutant-like status (RNA: 1.7%). Mutant-like TP53 (RNA) was strongly associated with age ≤50 years, high tumor grade, advanced stage of disease, large tumor size, and basal-like and HER2 intrinsic subtypes. Black race was strongly associated with TP53 mutant-like status (RNA) (RFD: 24.8%, 95% CI: 20.5, 29.0) even after adjusting for age, grade, stage (RFD: 11.3%; 95% CI: 7.6, 15.0). Associations were attenuated and non-significant when measured by IHC. IHC-based TP53 status is an insensitive measurement of TP53 functional status. RNA-based methods suggest a role for TP53 in tumor prognostic features and racial disparities. Nature Publishing Group UK 2018-06-25 /pmc/articles/PMC6018637/ /pubmed/29951581 http://dx.doi.org/10.1038/s41523-018-0067-5 Text en © The Author(s) 2018 Open Access 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 http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Williams, Lindsay A. Butler, Ebonee N. Sun, Xuezheng Allott, Emma H. Cohen, Stephanie M. Fuller, Ashley M. Hoadley, Katherine A. Perou, Charles M. Geradts, Joseph Olshan, Andrew F. Troester, Melissa A. TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases |
title | TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases |
title_full | TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases |
title_fullStr | TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases |
title_full_unstemmed | TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases |
title_short | TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases |
title_sort | tp53 protein levels, rna-based pathway assessment, and race among invasive breast cancer cases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018637/ https://www.ncbi.nlm.nih.gov/pubmed/29951581 http://dx.doi.org/10.1038/s41523-018-0067-5 |
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