TP53 mutation and abnormal p53 expression in endometrial cancer: Associations with race and outcomes

Karley Whelan, Mairead Dillon, Kyle C. Strickland, Bhavana Pothuri, Victoria Bae-Jump, Lindsay E. Borden, Premal H. Thaker, Paulina Haight, Rebecca C. Arend, Emily Ko, Amanda L. Jackson, Bradley R. Corr, Martins Ayoola-Adeola, Jason D. Wright, Sarah Podwika, Carson Smitherman, Samantha Thomas, Michelle Lightfoot, Meredith Newton, Christina WashingtonMary Mullen, Casey Cosgrove, Alfonsus Adrian Hadikusumo Harsono, Kristina Powell, Thomas J. Herzog, Ritu Salani, Angeles Alvarez Secord

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Objective: This multi-center cohort study assessed associations between race, TP53 mutations, p53 expression, and histology to investigate racial survival disparities in endometrial cancer (EC). Methods: Black and White patients with advanced or recurrent EC with Next Generation Sequencing data in the Endometrial Cancer Molecularly Targeted Therapy Consortium database were identified. Clinicopathologic and treatment variables were summarized by race and compared. Overall survival (OS) and progression-free survival (PFS) among all patients were estimated by the Kaplan-Meier method. Cox proportional hazards models estimated the association between race, TP53 status, p53 expression, histology, and survival outcomes. Results: Black patients were more likely than White patients to have TP53-mutated (N = 727, 71.7% vs 49.7%, p < 0.001) and p53-abnormal (N = 362, 71.1% vs 53.2%, p = 0.003) EC. Patients with TP53-mutated EC had worse PFS (HR 2.73 (95% CI 1.88–3.97)) and OS (HR 2.20 (95% CI 1.77–2.74)) compared to those with TP53-wildtype EC. Patients with p53-abnormal EC had worse PFS (HR 2.01 (95% CI 1.22–3.32)) and OS (HR 1.61 (95% CI 1.18–2.19)) compared to those with p53-wildtype EC. After adjusting for TP53 mutation and p53 expression, race was not associated with survival outcomes. The most frequent TP53 variants were at nucleotide positions R273 (n = 54), R248 (n = 38), and R175 (n = 23), rates of which did not differ by race. Conclusions: Black patients are more likely to have TP53-mutated and p53-abnormal EC, which are associated with worse survival outcomes than TP53- and p53-wildtype EC. The higher frequency of these subtypes among Black patients may contribute to survival disparities.

Original languageEnglish
Pages (from-to)44-53
Number of pages10
JournalGynecologic oncology
Volume178
DOIs
StatePublished - Nov 2023

Keywords

  • Abnormal p53 expression
  • And endometrial cancer
  • Heath disparities
  • Molecular subtypes
  • Survival
  • TP53 mutations

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