To identify the small group with Barrett’s esophagus (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 has precluded its use. To develop a robust criteria for grading abnormal immunochemical (IHC) expression of p53 and to test its utility as a biomarker for progression in BE, the following was carried out.
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 retrospective cohort, regardless of histologic diagnosis.
In a retrospective cohort, abnormal p53 was associated with a hazard ratio of 5.03 and hazard ratio of 5.27 for patients with exclusively nondysplastic disease before progression.
In a prospective validation cohort, p53 IHC predicted progression among nondysplastic BE, indefinite for dysplasia and low-grade dysplasia.
It was concluded that 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 biopsy of all BE patients without high-grade dysplasia or cancer.
Redston, M., Noffsinger, A., Kim, A., et al. “Abnormal TP53 Predicts Risk of Progression in Patients with Barrett’s Esophagus Regardless of a Diagnosis of Dysplasia.” Gastroenterology 2022; Vol. 162, pp. 468-481, February 2022.
Murray H. Cohen, DO, “From the Literature” Editor, is on the Editorial Board of Practical Gastroenterology.