Abstract
BACKGROUND AND AIMS: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.METHODS: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.RESULTS: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).CONCLUSIONS: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.
Highlights
AND AIMS: Barrett’s esophagus (BE) is the precursor to esophageal adenocarcinoma
After Institutional Review Board approval, the pathology records of Inform Diagnostics (Irving, TX), a national gastrointestinal pathology laboratory providing services to gastroenterologists throughout the United States, were searched from 2001 to 2011 to identify patients who were undergoing endoscopic surveillance for BE. These patients were divided into progressors and nonprogressors (Supplementary Methods)
There was no association detected between age at diagnosis and p53 IHC status (Supplementary Table 5)
Summary
AND AIMS: 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. 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. 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). Barrett’s esophagus is the premalignant lesion of esophageal adenocarcinoma but has a low rate of progression. Biomarkers that can identify patients at high and low risk of progression would greatly aid surveillance strategies
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