Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression

Systematic Review and Meta-Analyses

Patrick Snyder, Kerry E Dunbar, Daisha J. Cipher, Rhonda F Souza, Stuart J Spechler, Vani J.A. Konda

Research output: Contribution to journalReview article

Abstract

Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p <.001 (95% CI 2.79–5.27) and OR 5.95, p <.001 (95% CI 2.68–13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p <.001 (95% CI 9.35–32.08) and RR = 14.25, p <.001 (95% CI 6.76–30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

Original languageEnglish (US)
JournalDigestive Diseases and Sciences
DOIs
StatePublished - Jan 1 2019

Fingerprint

Barrett Esophagus
Meta-Analysis
Case-Control Studies
Cohort Studies
Biopsy
Selection Bias
Gastroenterology
Adenocarcinoma
Immunohistochemistry
Neoplasms

Keywords

  • Barrett’s esophagus
  • Biomarker
  • Esophageal adenocarcinoma
  • Immunohistochemistry
  • p53

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

@article{7b460987c5eb4b7d84133973f1de2ba0,
title = "Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses",
abstract = "Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p <.001 (95{\%} CI 2.79–5.27) and OR 5.95, p <.001 (95{\%} CI 2.68–13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p <.001 (95{\%} CI 9.35–32.08) and RR = 14.25, p <.001 (95{\%} CI 6.76–30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.",
keywords = "Barrett’s esophagus, Biomarker, Esophageal adenocarcinoma, Immunohistochemistry, p53",
author = "Patrick Snyder and Dunbar, {Kerry E} and Cipher, {Daisha J.} and Souza, {Rhonda F} and Spechler, {Stuart J} and Konda, {Vani J.A.}",
year = "2019",
month = "1",
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doi = "10.1007/s10620-019-05586-7",
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T1 - Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression

T2 - Systematic Review and Meta-Analyses

AU - Snyder, Patrick

AU - Dunbar, Kerry E

AU - Cipher, Daisha J.

AU - Souza, Rhonda F

AU - Spechler, Stuart J

AU - Konda, Vani J.A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p <.001 (95% CI 2.79–5.27) and OR 5.95, p <.001 (95% CI 2.68–13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p <.001 (95% CI 9.35–32.08) and RR = 14.25, p <.001 (95% CI 6.76–30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

AB - Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p <.001 (95% CI 2.79–5.27) and OR 5.95, p <.001 (95% CI 2.68–13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p <.001 (95% CI 9.35–32.08) and RR = 14.25, p <.001 (95% CI 6.76–30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

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KW - Esophageal adenocarcinoma

KW - Immunohistochemistry

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JO - Digestive Diseases and Sciences

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