{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:25:32Z","timestamp":1780568732745,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA81570"],"award-info":[{"award-number":["R01 CA81570"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The purpose of this study was to determine prospectively whether p53 protein accumulation in biopsies of Barrett's metaplasia (<jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content>) is a predictor of malignant progression, without relying on dysplasia grading.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Sections of formalin\u2010fixed paraffin\u2010embedded tissue from the initial biopsies of 275 patients with <jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content>, who had no high\u2010grade dysplasia (<jats:styled-content style=\"fixed-case\">HGD<\/jats:styled-content>) or oesophageal adenocarcinoma (<jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content>), were stained for p53 by immunohistochemistry. The mean follow\u2010up was 41 months. p53\u2010positive biopsies were divided into four groups: scattered positive cells, multifocal scattered positive cells, aggregates of positive cells, and multifocal aggregates of positive cells. Kaplan\u2013Meier analysis with the log\u2010rank test was used to determine the rate of progression to <jats:styled-content style=\"fixed-case\">HGD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content>. Of the 275 patients, 227 had initial biopsies that were completely negative for p53, and, of these, one (0.4%) progressed to <jats:styled-content style=\"fixed-case\">HGD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content>; none of 24 (0%) patients with scattered positive cells and none of four (0%) of patients with multifocal scattered positive cells progressed. In contrast, five of 16 (31.25%) patients with aggregates of positive cells and three of four (75%) of those with multifocal aggregates of positive cells progressed to <jats:styled-content style=\"fixed-case\">HGD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content>. Kaplan\u2013Meier analysis with log\u2010rank statistics showed the difference in progression rate between the five groups to be highly significant (<jats:italic>P<\/jats:italic> &lt; 0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that p53 protein accumulation, detected by immunohistochemistry in aggregates of cells, is a significant predictor of malignant progression in patients with <jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13193","type":"journal-article","created":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T20:22:42Z","timestamp":1487794962000},"page":"27-33","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["p53 protein accumulation predicts malignant progression in Barrett's metaplasia: a prospective study of 275 patients"],"prefix":"10.1111","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9618-3451","authenticated-orcid":false,"given":"Mamoun","family":"Younes","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Texas Health Science Center at Houston McGovern Medical School, and Memorial Hermann Hospital\u2010TMC Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pathology Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y","family":"Lauwers","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology H. Lee Moffitt Cancer Center Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulchin","family":"Ergun","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology Department of Medicine Houston Methodist Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Meriano","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology Department of Medicine Houston Methodist Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Carl","family":"Schmulen","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology Department of Medicine Houston Methodist Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Barroso","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology Department of Medicine Houston Methodist Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atilla","family":"Ertan","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology, Hepatology and Nutrition Department of Medicine University of Texas Health Science Center at Houston McGovern Medical School, and Memorial Hermann Hospital\u2010TMC Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1998.00362.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.05910.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2008.01835.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800750813"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.3.378"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2014.156"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307197"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308802"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12913"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(88)80344-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2001.23510"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181ffdd14"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2010.03571.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)91058-P"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018828207371"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/003655200750024281"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/003655202762671215"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2050.2010.01054.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.2"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.171"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-7404(10)80021-0"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.46.4.330"},{"key":"e_1_2_8_24_1","first-page":"211","article-title":"Detection of the risk of adenocarcinoma in Barrett's esophagus by means of tumor markers (p53 and Ki67)","volume":"40","author":"Trakal E","year":"2010","journal-title":"Acta Gastroenterol. Latinoam."},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/00313029800169076"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711750204"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018891923998"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/S0022-5223(12)70179-4","article-title":"p53 immunoreactivity in Barrett's metaplasia, dysplasia, and carcinoma","volume":"108","author":"Rice TW","year":"1994","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(94)90225-9"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2001.03851.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2009.03288.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.437"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/gov045"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.06032.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303594"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12956"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.083295"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2004.tb05991.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2004.30228.x"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03579.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.06.001"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.11.014"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2013.07.020"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.13193","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.13193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T02:21:25Z","timestamp":1696299685000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.13193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,11]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1111\/his.13193"],"URL":"https:\/\/doi.org\/10.1111\/his.13193","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,11]]},"assertion":[{"value":"2016-11-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}