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Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses
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 n...
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Published in: | Digestive diseases and sciences 2019-05, Vol.64 (5), p.1089-1097 |
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description | 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
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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.</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1007/s10620-019-05586-7</identifier><identifier>PMID: 30911864</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adenocarcinoma - diagnosis ; Adenocarcinoma - metabolism ; Analysis ; Antimitotic agents ; Antineoplastic agents ; Barrett Esophagus - diagnosis ; Barrett Esophagus - metabolism ; Biochemistry ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - immunology ; Case-Control Studies ; Development and progression ; Disease Progression ; Dysplasia ; Esophageal cancer ; Esophageal Neoplasms - diagnosis ; Esophageal Neoplasms - metabolism ; Esophagus ; Gastroenterology ; Health risk assessment ; Hepatology ; Histopathology ; Humans ; Immunohistochemistry ; Medical research ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Meta-analysis ; Oncology ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Retrospective Studies ; Review ; Sampling error ; Staining and Labeling - methods ; Systematic review ; Transplant Surgery ; Tumor proteins ; Tumor Suppressor Protein p53 - analysis ; Tumor Suppressor Protein p53 - biosynthesis ; Tumor Suppressor Protein p53 - immunology</subject><ispartof>Digestive diseases and sciences, 2019-05, Vol.64 (5), p.1089-1097</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>COPYRIGHT 2019 Springer</rights><rights>Digestive Diseases and Sciences is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-9508423478b08cc61df82dd4c693d2ad66e2f32415e80aae7dc1310de5364f203</citedby><cites>FETCH-LOGICAL-c442t-9508423478b08cc61df82dd4c693d2ad66e2f32415e80aae7dc1310de5364f203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30911864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Snyder, Patrick</creatorcontrib><creatorcontrib>Dunbar, Kerry</creatorcontrib><creatorcontrib>Cipher, Daisha J.</creatorcontrib><creatorcontrib>Souza, Rhonda F.</creatorcontrib><creatorcontrib>Spechler, Stuart Jon</creatorcontrib><creatorcontrib>Konda, Vani J. A.</creatorcontrib><title>Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><addtitle>Dig Dis Sci</addtitle><description>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.</description><subject>Adenocarcinoma - diagnosis</subject><subject>Adenocarcinoma - metabolism</subject><subject>Analysis</subject><subject>Antimitotic agents</subject><subject>Antineoplastic agents</subject><subject>Barrett Esophagus - diagnosis</subject><subject>Barrett Esophagus - metabolism</subject><subject>Biochemistry</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Biomarkers, Tumor - immunology</subject><subject>Case-Control Studies</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Dysplasia</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - diagnosis</subject><subject>Esophageal Neoplasms - metabolism</subject><subject>Esophagus</subject><subject>Gastroenterology</subject><subject>Health risk assessment</subject><subject>Hepatology</subject><subject>Histopathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Experimental</subject><subject>Meta-analysis</subject><subject>Oncology</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Review</subject><subject>Sampling error</subject><subject>Staining and Labeling - methods</subject><subject>Systematic review</subject><subject>Transplant Surgery</subject><subject>Tumor proteins</subject><subject>Tumor Suppressor Protein p53 - analysis</subject><subject>Tumor Suppressor Protein p53 - biosynthesis</subject><subject>Tumor Suppressor Protein p53 - immunology</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1TAQhSMEopfCC7BAkdiwSfHYiZOwu1QFKpUf8bO2fO3JxVViB48Dujteg9fjSUhIoQIh5IWt4-8czehk2X1gJ8BY_ZiASc4KBm3BqqqRRX0j20BVi4JXsrmZbRjI-Q0gj7I7RJeMsbYGeTs7EqwFaGS5yQ7bHcaofcrHSuTnwzD5QEk77_w-dz5_qmPElL5__Ub5GYXxo95PlL-JaJ1JlL_CMPaakjOzFvYRiVzwT_J3B0o46EV_i58dfsm1t_lLTLrYet0fCOludqvTPeG9q_s4-_Ds7P3pi-Li9fPz0-1FYcqSp6KtWFNyUdbNjjXGSLBdw60tjWyF5dpKibwTvIQKG6Y11taAAGaxErLsOBPH2aM1d4zh04SU1ODIYN9rj2EixaGtm6YFVs_ow7_QyzDFed6VYiVILq6pve5ROd-FFLVZQtW2Bt6KGsol6-Qf1HwsDs4Ej52b9T8MfDWYGIgidmqMbtDxoICppW-19q3mvtXPvtVienA18bQb0P62_Cp4BsQK0Pzl9xivV_pP7A-OubU7</recordid><startdate>20190501</startdate><enddate>20190501</enddate><creator>Snyder, Patrick</creator><creator>Dunbar, Kerry</creator><creator>Cipher, Daisha J.</creator><creator>Souza, Rhonda F.</creator><creator>Spechler, Stuart Jon</creator><creator>Konda, Vani J. A.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20190501</creationdate><title>Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses</title><author>Snyder, Patrick ; Dunbar, Kerry ; Cipher, Daisha J. ; Souza, Rhonda F. ; Spechler, Stuart Jon ; Konda, Vani J. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-9508423478b08cc61df82dd4c693d2ad66e2f32415e80aae7dc1310de5364f203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenocarcinoma - diagnosis</topic><topic>Adenocarcinoma - metabolism</topic><topic>Analysis</topic><topic>Antimitotic agents</topic><topic>Antineoplastic agents</topic><topic>Barrett Esophagus - diagnosis</topic><topic>Barrett Esophagus - metabolism</topic><topic>Biochemistry</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomarkers, Tumor - immunology</topic><topic>Case-Control Studies</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>Dysplasia</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - diagnosis</topic><topic>Esophageal Neoplasms - metabolism</topic><topic>Esophagus</topic><topic>Gastroenterology</topic><topic>Health risk assessment</topic><topic>Hepatology</topic><topic>Histopathology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medicine, Experimental</topic><topic>Meta-analysis</topic><topic>Oncology</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>Review</topic><topic>Sampling error</topic><topic>Staining and Labeling - methods</topic><topic>Systematic review</topic><topic>Transplant Surgery</topic><topic>Tumor proteins</topic><topic>Tumor Suppressor Protein p53 - analysis</topic><topic>Tumor Suppressor Protein p53 - biosynthesis</topic><topic>Tumor Suppressor Protein p53 - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Snyder, Patrick</creatorcontrib><creatorcontrib>Dunbar, Kerry</creatorcontrib><creatorcontrib>Cipher, Daisha J.</creatorcontrib><creatorcontrib>Souza, Rhonda F.</creatorcontrib><creatorcontrib>Spechler, Stuart Jon</creatorcontrib><creatorcontrib>Konda, Vani J. A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Databases</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Family Health Database (Proquest)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Snyder, Patrick</au><au>Dunbar, Kerry</au><au>Cipher, Daisha J.</au><au>Souza, Rhonda F.</au><au>Spechler, Stuart Jon</au><au>Konda, Vani J. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses</atitle><jtitle>Digestive diseases and sciences</jtitle><stitle>Dig Dis Sci</stitle><addtitle>Dig Dis Sci</addtitle><date>2019-05-01</date><risdate>2019</risdate><volume>64</volume><issue>5</issue><spage>1089</spage><epage>1097</epage><pages>1089-1097</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30911864</pmid><doi>10.1007/s10620-019-05586-7</doi><tpages>9</tpages></addata></record> |
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subjects | Adenocarcinoma - diagnosis Adenocarcinoma - metabolism Analysis Antimitotic agents Antineoplastic agents Barrett Esophagus - diagnosis Barrett Esophagus - metabolism Biochemistry Biomarkers, Tumor - analysis Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - immunology Case-Control Studies Development and progression Disease Progression Dysplasia Esophageal cancer Esophageal Neoplasms - diagnosis Esophageal Neoplasms - metabolism Esophagus Gastroenterology Health risk assessment Hepatology Histopathology Humans Immunohistochemistry Medical research Medicine Medicine & Public Health Medicine, Experimental Meta-analysis Oncology Predictive Value of Tests Prognosis Prospective Studies Retrospective Studies Review Sampling error Staining and Labeling - methods Systematic review Transplant Surgery Tumor proteins Tumor Suppressor Protein p53 - analysis Tumor Suppressor Protein p53 - biosynthesis Tumor Suppressor Protein p53 - immunology |
title | Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses |
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