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Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses

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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.

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Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX, 75246, USA

    Patrick Snyder, Rhonda F. Souza, Stuart Jon Spechler & Vani J. A. Konda

  2. Esophageal Diseases Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Kerry Dunbar

  3. Veterans Affairs North Texas Health Care System, 4500 S. Lancaster Road, Dallas, TX, 75216, USA

    Kerry Dunbar

  4. College of Nursing and Health Innovation, University of Texas at Arlington, 701 S. Nedderman Drive, Mailbox 19407, Arlington, TX, 76019, USA

    Daisha J. Cipher

  5. Center for Esophageal Diseases, Baylor University Medical Center, Dallas, TX, USA

    Rhonda F. Souza, Stuart Jon Spechler & Vani J. A. Konda

  6. Center for Esophageal Research, Baylor Scott & White Research Institute, Dallas, TX, USA

    Rhonda F. Souza, Stuart Jon Spechler & Vani J. A. Konda

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  1. Patrick Snyder
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Contributions

PS collected, analyzed, and interpreted the data, and drafted the manuscript. KD and RFS analyzed and interpreted the data, and critically revised the manuscript for important intellectual content. SJS conceived the topic, analyzed and interpreted the data, and critically revised the manuscript for important intellectual content. DJC evaluated the performance of statistical analyses and critically revised the manuscript for important intellectual content. VJAK conceived the topic, analyzed and interpreted the data, critically revised the manuscript for important intellectual content, and was responsible for the final approval.

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Correspondence to Vani J. A. Konda.

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Conflict of interest

Rhonda F. Souza has served as a consultant and receives research support from Ironwood Pharmaceuticals. Stuart Jon Spechler has served as a consultant for Ironwood Pharmaceuticals. Vani J.A. Konda has received grant support from Pentax Medical and Ironwood Pharmaceuticals. Patrick Snyder, Kerry Dunbar, and Daisha J. Cipher have no conflict of interest.

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Snyder, P., Dunbar, K., Cipher, D.J. et al. Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses. Dig Dis Sci 64, 1089–1097 (2019). https://doi.org/10.1007/s10620-019-05586-7

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