TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases.

Published online

Journal 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.

Full Text

Duke Authors

Cited Authors

  • Williams, LA; Butler, EN; Sun, X; Allott, EH; Cohen, SM; Fuller, AM; Hoadley, KA; Perou, CM; Geradts, J; Olshan, AF; Troester, MA

Published Date

  • 2018

Published In

Volume / Issue

  • 4 /

Start / End Page

  • 13 -

PubMed ID

  • 29951581

Pubmed Central ID

  • 29951581

International Standard Serial Number (ISSN)

  • 2374-4677

Digital Object Identifier (DOI)

  • 10.1038/s41523-018-0067-5

Language

  • eng

Conference Location

  • United States