Evidence map›Paper›PMID 34757142›Full record

ArticleGastroenterology2022

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

Mark Redston, Amy Noffsinger, Anthony Kim, Fahire G Akarca, Marianne Rara, Diane Stapleton, Laurel Nowden, Richard Lash, Adam J Bass, Matthew D Stachler

Open access · hybridAbstract read
In one paragraph

Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 2 pooled it
11.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 90 citations in OpenAlex.

  1. Guideline
  2. AGA Clinical Practice Update on New Technology and Innovation for Surveillance and Screening in Barrett's Esophagus: Expert Review.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2022
    Guideline
  3. Article
  4. Article
  5. Review
  6. Biomarker Use in Barrett's Esophagus Surveillance.The American journal of gastroenterology · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Emerging Biomarkers for Managing Barrett's Esophagus.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  11. Current Concepts for Diagnosing Non-Dysplastic and Dysplastic Barrett's Esophagus.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  12. Review
  13. Pathogenesis of Barrett's Esophagus: Evolving and Emerging Mechanisms.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Mark RedstonDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: mredston@partners.org.
Amy NoffsingerInform Diagnostics, Irving, Texas.
Anthony KimDepartment of Molecular Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
Fahire G AkarcaDepartment of Molecular Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
Marianne RaraDepartment of Pathology, University of California San Francisco, San Francisco, California.
Diane StapletonInform Diagnostics, Irving, Texas.
Laurel NowdenInform Diagnostics, Irving, Texas.
Richard LashR Lash MD, LLC, Southlake, Texas.
Adam J BassDepartment of Molecular Oncology, Dana Farber Cancer Institute, Boston, Massachusetts; Eli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Matthew D StachlerDepartment of Pathology, University of California San Francisco, San Francisco, California. Electronic address: Matthew.Stachler@UCSF.edu.
Molecular Oncology (United States) · USUniversity of California, San Francisco · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · US

Funding

Whole Exome Approaches for Esophageal Adenocarcinoma Susceptibility GenesU54CA163060 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI CHAK, AMITABH, GUDA, KISHORE · 2011 to 2022
$14.0M
Early TP53 Mutations and Genomic Doubling as a Novel Path for Barrett's Esophagus ProgressionK08DK109209 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STACHLER, MATTHEW D · 2016 to 2021
$929k
Doris Duke Charitable Foundation 2018089NCI NIH HHS U54 CA163060NIDDK NIH HHS K08 DK109209
6 · The paper itself

Abstract

BACKGROUND AND

aimsBarrett'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.

methodsCriteria 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.

resultsAbnormal 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).

conclusionsp53 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.

Indexed as

AdenocarcinomaAdultAgedAged, 80 and overBarrett EsophagusDisease ProgressionEsophageal NeoplasmsFemaleHumansImmunohistochemistryMaleMiddle AgedPrognosisRisk AssessmentTumor Suppressor Protein p53TP53 protein, humanTumor Suppressor Protein p53Barrett’s EsophagusCancer Risk StratificationSurveillanceTP53

Identifiers

PMID34757142
PMCPMC9341495
OpenAlexW3161902267

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.