{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:34:26Z","timestamp":1792290866323,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T00:00:00Z","timestamp":1375747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Epithelial dysplasia is an important histological diagnosis signifying the presence of pre\u2010invasive disease, usually needing intervention. However, the specific genetic changes responsible for the induction of this phenotypic change are unknown. Moreover, recent reports indicate that the dysplastic phenotype may not be immutable: in basal crypt dysplasia (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>), unequivocal dysplastic changes are seen in the crypts in Barrett's oesophagus and other pre\u2010invasive lesions in the gastrointestinal tract, but the upper crypts and surface epithelium associated with these dysplastic crypts show the definitive morphology of a differentiated epithelium. The genotypic relationship between <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content> and the differentiated surface epithelium is presently unclear. We obtained 17 examples of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>: the lower and upper crypts and surface epithelium were differentially laser\u2010microdissected from formalin\u2010fixed, paraffin\u2010embedded sections and mutations were sought in tumour suppressor genes frequently associated with progression in Barrett's oesophagus. We found two patients who both showed a c. <jats:styled-content style=\"fixed-case\">C238T<\/jats:styled-content> mutation in the <jats:italic><jats:styled-content style=\"fixed-case\">CDKN2A<\/jats:styled-content><\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>KN2A<\/jats:italic>Ink4A) gene and where the precise microanatomical relationships could be discerned: this mutation was present in both the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content> at the crypt base and in the upper crypt and surface epithelium. We conclude that, in CD, the dysplastic basal crypt epithelium and the upper crypt and surface epithelium show clonal <jats:italic><jats:styled-content style=\"fixed-case\">CDKN2A<\/jats:styled-content><\/jats:italic> mutations, thus showing definitively that the surface epithelium is derived from the dysplastic crypt epithelium: the dysplastic phenotype is therefore not fixed and can be reversed. The mechanism of this change is unclear but may be related to the possibility that dysplastic cells can, probably early in their progression, respond to differentiation signals. However, it is also clear that a heavy mutational burden can be borne by crypts in the gastrointestinal tract without the development of phenotypic dysplasia. We are evidently some way from understanding the plasticity and the genotypic correlates of the dysplastic phenotype. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4211","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T14:09:03Z","timestamp":1369145343000},"page":"98-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Crypt dysplasia in Barrett's oesophagus shows clonal identity between crypt and surface cells"],"prefix":"10.1002","volume":"231","author":[{"given":"Shabuddin","family":"Khan","sequence":"first","affiliation":[{"name":"Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine and Dentistry Queen Mary University of London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart AC","family":"McDonald","sequence":"additional","affiliation":[{"name":"Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine and Dentistry Queen Mary University of London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A","family":"Wright","sequence":"additional","affiliation":[{"name":"Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine and Dentistry Queen Mary University of London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor A","family":"Graham","sequence":"additional","affiliation":[{"name":"Center for Evolution and Cancer University of California at San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D","family":"Odze","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rodriguez\u2010Justo","sequence":"additional","affiliation":[{"name":"Department of Histopathology University College Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Zeki","sequence":"additional","affiliation":[{"name":"Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine and Dentistry Queen Mary University of London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.041525"},{"key":"e_1_2_7_3_1","first-page":"657","article-title":"Pathogenetic mechanisms of nuclear pleomorphism of tumour cells based on the mutator phenotype theory of carcinogenesis","volume":"18","author":"Bignold L.","year":"2003","journal-title":"Histol Histopathol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(83)80175-0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(88)80344-7"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.5858\/134.6.896"},{"issue":"1","key":"e_1_2_7_7_1","first-page":"168A","article-title":"Risk of conventional dysplasia and adenocarcinoma in patients with Barrett's esophagus and crypt dysplasia: a prospective follow\u2010up study of 214 patients","volume":"23","author":"Srivastava A","year":"2010","journal-title":"Mod Pathol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200604000-00001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181ffdd14"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.143339"},{"key":"e_1_2_7_11_1","first-page":"1251","article-title":"Rodriguez\u2010Justo M","volume":"140","author":"Gutierrez\u2010Gonzalez L Graham","year":"2011","journal-title":"Al. 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