Dataset Information

Detection of Mutations in Barrett's Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma.

ABSTRACT: BACKGROUND & AIMS:Barrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma (EAC), but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress. METHODS:We performed a retrospective case-control study of 24 patients with BE that progressed to high-grade dysplasia (HGD, n = 14) or EAC (n = 10). The control group (n = 73, called non-progressors) comprised patients with BE and at least 5 years of total endoscopic biopsy surveillance without progression to HGD or EAC. From each patient, we selected a single tissue sample obtained more than 1 year before progression (cases) or more than 2 years before the end of follow-up (controls). Pathogenic mutations, gene copy numbers, and ploidy were compared between samples from progressors and non-progressors. RESULTS:TP53 mutations were detected in 46% of samples from progressors and 5% of non-progressors. In this case-control sample set, TP53 mutations in BE tissues increased the adjusted risk of progression 13.8-fold (95% confidence interval, 3.2-61.0) (P < .001). We did not observe significant differences in ploidy or copy-number profile between groups. We identified 147 pathogenic mutations in 57 distinct genes-the average number of pathogenic mutations was higher in samples from progressors (n = 2.5) than non-progressors (n = 1.2) (P < .001). TP53 and other somatic mutations were recurrently detected in samples with limited copy-number changes (aneuploidy). CONCLUSIONS:In genomic analyses of BE tissues from patients with or without later progression to HGD or EAC, we found significantly higher numbers of TP53 mutations in BE from patients with subsequent progression. These mutations were frequently detected before the onset of dysplasia or substantial changes in copy number.

SUBMITTER: Stachler MD

PROVIDER: S-EPMC6035092 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Detection of Mutations in Barrett's Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma.

Stachler Matthew D MD Camarda Nicholas D ND Deitrick Christopher C Kim Anthony A Agoston Agoston T AT Odze Robert D RD Hornick Jason L JL Nag Anwesha A Thorner Aaron R AR Ducar Matthew M Noffsinger Amy A Lash Richard H RH Redston Mark M Carter Scott L SL Davison Jon M JM Bass Adam J AJ

Gastroenterology 20180331 1

<h4>Background & aims</h4>Barrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma (EAC), but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress.<h4>Methods</h4>We performed a retrospective case-control study of 24 pa ...[more]

PMID: 29608884

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Project description:IntroductionEndoscopic eradication therapy with radiofrequency ablation (RFA) and endoscopic mucosal resection is a safe and effective treatment for Barrett's esophagus. Although the outcomes of surveillance endoscopy after successful endoscopic eradication therapy have been described, no previous studies have modeled the natural history or the effect of surveillance endoscopy after successful ablation to prevent progression to invasive esophageal adenocarcinoma.MethodsThe US RFA Registry is a multicenter registry consisting of patients treated with RFA for Barrett's esophagus at 148 institutions (113 community-based and 35 academic-affiliated). The authors fit models to impute the natural history of recurrence and neoplastic progression after any recurrence or retreatment. Natural history estimates of invasive adenocarcinoma after ablation therapy were compared with as-treated estimates at 5 years to derive the preventive risk difference for surveillance.ResultsNatural history estimates for the postablation progression of high-grade dysplasia (HGD) or intramucosal adenocarcinoma to invasive adenocarcinoma after treatment were 6.3% at 5 years compared with 1.3% for low-grade dysplasia (LGD). The natural history model found a much higher preventative risk difference for surveillance for HGD/intramucosal adenocarcinoma (-4.8%), compared with LGD (-1.1%). The numbers needed to surveil at 5 years were 21 and 90 for these groups, respectively, to prevent one case of invasive esophageal adenocarcinoma, making surveillance after successful ablation of baseline HGD more than 4 times as effective at preventing invasive cancer than after successful ablation of baseline LGD.DiscussionEndoscopic surveillance after successful ablation of baseline HGD or intramucosal cancer is much more effective than surveillance after successful treatment of baseline LGD in averting invasive adenocarcinoma. Although the modest benefits of surveillance for treated LGD may be greater than the risks for patients at average risk for adverse effects of endoscopy, clinicians should concentrate on retaining patients with baseline HGD or cancer in endoscopic surveillance programs.

Project description:INTRODUCTION:Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE-associated dysplasia on index endoscopy over the past 25 years. METHODS:The Barrett's Esophagus Study is a multicenter outcome project of a large cohort of patients with BE. Proportions of patients with index endoscopy findings of no dysplasia (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC were extracted per year of index endoscopy, and 5-yearly patient cohorts were tabulated over years 1990 to 2010+ (2010-current). Prevalent dysplasia and endoscopic findings were trended over the past 25 years using percentage dysplasia (LGD, HGD, EAC, and HGD/EAC) to assess changes in detection of BE-associated dysplasia over the last 25 years. Statistical analysis was done using SAS version 9.4 software (SAS, Cary, NC). RESULTS:A total of 3643 patients were included in the analysis with index endoscopy showing NDBE in 2513 (70.1%), LGD in 412 (11.5%), HGD in 193 (5.4%), and EAC in 181 (5.1%). Over time, there was an increase in the mean age of patients with BE (51.7 ± 29 years vs 62.6 ± 11.3 years) and the proportion of males (84% vs 92.6%) diagnosed with BE but a decrease in the mean BE length (4.4±4.3 cm vs 2.9±3.0 cm) as time progressed (1990-1994 to 2010-2016 time periods). The presence of LGD on index endoscopy remained stable over 1990 to 2016. However, a significant increase (148% in HGD and 112% in EAC) in the diagnosis of HGD, EAC, and HGD/EAC was noted on index endoscopy over the last 25 years (P < .001). There was also a significant increase in the detection of visible lesions on index endoscopy (1990-1994, 5.1%; to 2005-2009, 6.3%; and 2010+, 16.3%) during the same period. CONCLUSION:Our results suggest that the prevalence of HGD and EAC has significantly increased over the past 25 years despite a decrease in BE length during the same period. This increase parallels an increase in the detection of visible lesions, suggesting that a careful examination at the index examination is crucial.

Dataset Information

Detection of Mutations in Barrett's Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma.

Publications

Detection of Mutations in Barrett's Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma.

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