# Abnormal TP53 Predicts Risk of Progression in Patients With Barrett’s Esophagus Regardless of a Diagnosis of Dysplasia

## TL;DR

Abnormal TP53 protein levels in Barrett’s esophagus biopsies can predict cancer progression risk, even in patients without dysplasia.

## Contribution

A robust and validated IHC-based TP53 biomarker for predicting progression in Barrett’s esophagus is developed and prospectively validated.

## Key findings

- Abnormal p53 IHC correlated strongly with TP53 mutations and predicted progression in BE patients.
- p53 IHC was effective in predicting progression even in patients with nondysplastic Barrett’s esophagus.
- Prospective validation confirmed p53 IHC's utility in clinical practice for risk stratification.

## Abstract

Barrett’s esophagus (BE) is the precursor to esophageal adenocarcinoma. A major challenge is identifying the small group with BE who will progress to advanced disease from the many who will not. Assessment of p53 status has promise as a predictive biomarker, but analytic limitations and lack of validation have precluded its use. The aim of this study was to develop a robust criteria for grading abnormal immunohistochemical (IHC) expression of p53 and to test its utility as a biomarker for progression in BE.

Criteria for abnormal IHC of p53 were developed in BE biopsies and validated with sequencing to assess TP53 mutations. The utility of p53 IHC as a biomarker for progression of BE was tested retrospectively in 561 patients with BE with or without known progression. The findings were prospectively validated in a clinical practice setting in 1487 patients with BE.

Abnormal p53 IHC highly correlated with TP53 mutation status (90.6% agreement) and was strongly associated with neoplastic progression in the retrospective cohorts, regardless of histologic diagnosis (P < .001). In the retrospective cohort, abnormal p53 was associated with a hazard ratio of 5.03 (95% confidence interval, 3.88–6.5) and a hazard ratio of 5.27 (95% confidence interval, 3.93–7.07) for patients with exclusively nondysplastic disease before progression. In the prospective validation cohort, p53 IHC predicted progression among nondysplastic BE, indefinite for dysplasia, and low-grade dysplasia (P < .001).

p53 IHC identifies patients with BE at higher risk of progression, including in patients without evidence of dysplasia. p53 IHC is inexpensive, easily integrated into routine practice, and should be considered in biopsies from all BE patients without high-grade dysplasia or cancer.