clinendoКлиническая эндоскопияFilin’s Clinical endoscopy2415-7813"Global Media technology" Ltd10.31146/2415-7813-endo-67-2-51-67clinendo-228Research ArticleГАСТРОЭНТЕРОЛОГИЯGASTROENTEROLOGYПатогенез и морфологическая диагностика ГЭРБ, НЭРБ и пищевода БарреттаPathogenesis and histological diagnostics of gerd, nerd and barrett’s esophagushttps://orcid.org/0000-0003-2052-914XМихалеваЛ. М.MikhalevaL. M.noemail@neicon.ruhttps://orcid.org/0000-0001-8083-9428МаслёнкинаК. С.MaslenkinaK. S.ksusha-voi@yandex.ruhttps://orcid.org/0009-0007-9071-1613НауменкоМ. С.NaumenkoM. S.noemail@neicon.ruhttps://orcid.org/0000-0002-1041-8561ГущинМ. Ю.GushchinM. Yu.noemail@neicon.ruhttps://orcid.org/0000-0001-5925-5196КонюковаА. К.KonyukovaA. K.noemail@neicon.ru«Научно-исследовательский институт морфологии человека имени академика А. П. Авцына» Федерального государственного бюджетного научного учреждения «Российский научный центр хирургии имени академика Б. В. Петровского»Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution «Petrovsky National Research Centre of Surgery»2025040920256725167Copyright © Михалева Л.М., Маслёнкина К.С., Науменко М.С., Гущин М.Ю., Конюкова А.К., 20252025Михалева Л.М., Маслёнкина К.С., Науменко М.С., Гущин М.Ю., Конюкова А.К.Mikhaleva L.M., Maslenkina K.S., Naumenko M.S., Gushchin M.Y., Konyukova A.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://clinendo.elpub.ru/jour/article/view/228

Диагностика воспалительных и предраковых заболеваний пищевода является клинико-морфологической и включает в себя морфологическую верификацию эндоскопических изменений в соответствии со специально разработанными протоколами взятия биопсийного материала в зависимости от эндоскопических находок и предполагаемого диагноза. Данная обзорная статья подробно рассматривает патогенез спектра гастроэзофагеальной рефлюксной болезни (ГЭРБ) и посвящена тонкостям морфологической диагностики пищевода Барретта (ПБ) и дисплазии при ПБ. Точная морфологическая диагностика у этой группы пациентов определяет тактику лечения и прогноз.

Since inflammatory diseases and precancerous lesions of esophagus require clinico-morphological diagnostics, it includes histological verification of endoscopic lesions in line with specific protocols of biopsy taking according to endoscopic findings and expected diagnosis. This review elucidates pathogenesis of gastroesophageal reflux disease (GERD) specter and focuses on detailed features of histologic diagnostics of Barrett’s esophagus and Barrett’s dysplasia. Precise histologic diagnosis in this group of patients implies appropriate treatment and defines prognosis.

гастроэзофагеальная рефлюксная болезньрефлюкс-эзофагитпищевод Барреттадисплазияиммуногистохимическое исследованиеp53gastroesophageal reflux diseasereflux esophagitisBarrett’s esophagusdysplasiaimmunohistochemical evaluationp53ReferencesVakil N., van Zanten S.V., Kahrilas P., Dent J., Jones R.; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20; quiz 1943. doi: 10.1111/j.1572-0241.2006.00630.x.Vakil N., van Zanten S.V., Kahrilas P., Dent J., Jones R.; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20; quiz 1943. doi: 10.1111/j.1572-0241.2006.00630.x.Gyawali C.P., Kahrilas P.J., Savarino E. et al. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018 Jul;67(7):1351-1362. doi: 10.1136/gutjnl-2017-314722.Gyawali C.P., Kahrilas P.J., Savarino E. et al. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018 Jul;67(7):1351-1362. doi: 10.1136/gutjnl-2017-314722.Gyawali C.P., Yadlapati R., Fass R. et al. Updates to the modern diagnosis of GERD: Lyon consensus 2.0. Gut. 2024 Jan 5;73(2):361-371. doi: 10.1136/gutjnl-2023-330616.Gyawali C.P., Yadlapati R., Fass R. et al. Updates to the modern diagnosis of GERD: Lyon consensus 2.0. Gut. 2024 Jan 5;73(2):361-371. doi: 10.1136/gutjnl-2023-330616.Biswas S, Quante M., Leedham S., Jansen M. The metaplastic mosaic of Barrett’s oesophagus. Virchows Archiv. 2018;472:43-54. doi: 10.1007/s00428-018-2317-1.Biswas S, Quante M., Leedham S., Jansen M. The metaplastic mosaic of Barrett’s oesophagus. Virchows Archiv. 2018;472:43-54. doi: 10.1007/s00428-018-2317-1.Maslenkina K., Mikhaleva L., Naumenko M. et al. Signaling Pathways in the Pathogenesis of Barrett’s Esophagus and Esophageal Adenocarcinoma.Int J Mol Sci. 2023; 24(11):9304. doi: 10.3390/ijms24119304.Maslenkina K., Mikhaleva L., Naumenko M. et al. Signaling Pathways in the Pathogenesis of Barrett’s Esophagus and Esophageal Adenocarcinoma.Int J Mol Sci. 2023; 24(11):9304. doi: 10.3390/ijms24119304.Wright N.A. Aspects of the biology of regeneration and repair in the human gastrointestinal tract. Philos Trans R Soc Lond Ser B Biol Sci. 1998;353(1370):925-933. doi: 10.1098/rstb.1998.0257.Wright N.A. Aspects of the biology of regeneration and repair in the human gastrointestinal tract. Philos Trans R Soc Lond Ser B Biol Sci. 1998;353(1370):925-933. doi: 10.1098/rstb.1998.0257.Evans J.A., Carlotti E., Lin M.L. et al. Clonal Transitions and Phenotypic Evolution in Barrett’s Esophagus. Gastroenterology. 2022 Apr;162(4):1197-1209.e13. doi: 10.1053/j.gastro.2021.12.271.Evans J.A., Carlotti E., Lin M.L. et al. Clonal Transitions and Phenotypic Evolution in Barrett’s Esophagus. Gastroenterology. 2022 Apr;162(4):1197-1209.e13. doi: 10.1053/j.gastro.2021.12.271.Quante M., Bhagat G., Abrams J.A. et al. Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell. 2012;21(1):36-51. doi: 10.1016/j.ccr.2011.12.004.Quante M., Bhagat G., Abrams J.A. et al. Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell. 2012;21(1):36-51. doi: 10.1016/j.ccr.2011.12.004.Kunze B., Wein F., Fang H.Y. et al. Notch Signaling Mediates Differentiation in Barrett’s Esophagus and Promotes Progression to Adenocarcinoma. Gastroenterology. 2020;159(2):575-90. doi: 10.1053/j.gastro.2020.04.033.Kunze B., Wein F., Fang H.Y. et al. Notch Signaling Mediates Differentiation in Barrett’s Esophagus and Promotes Progression to Adenocarcinoma. Gastroenterology. 2020;159(2):575-90. doi: 10.1053/j.gastro.2020.04.033.Lavery D.L., Nicholson A.M., Poulsom R. et al. The stem cell organisation, and the proliferative and gene expression profile of Barrett’s epithelium, replicates pyloric-type gastric glands. Gut. 2014;63(12):1854-63. doi: 10.1136/gutjnl-2013-306508.Lavery D.L., Nicholson A.M., Poulsom R. et al. The stem cell organisation, and the proliferative and gene expression profile of Barrett’s epithelium, replicates pyloric-type gastric glands. Gut. 2014;63(12):1854-63. doi: 10.1136/gutjnl-2013-306508.McDonald S.A., Lavery D., Wright N.A., Jansen M. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol. 2015;12(1):50-60.McDonald S.A., Lavery D., Wright N.A., Jansen M. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol. 2015;12(1):50-60.Nomura S., Goldenring J.R. Mind the Gap: Crossing Boundaries to Establish Reparative Metaplasia. Cell Mol Gastroenterol Hepatol. 2018 Aug 8;6(4):468-469. doi: 10.1016/j.jcmgh.2018.07.002.Nomura S., Goldenring J.R. Mind the Gap: Crossing Boundaries to Establish Reparative Metaplasia. Cell Mol Gastroenterol Hepatol. 2018 Aug 8;6(4):468-469. doi: 10.1016/j.jcmgh.2018.07.002.Goldenring J.R. Pyloric metaplasia, pseudopyloric metaplasia, ulcer-associated cell lineage and spasmolytic polypeptide-expressing metaplasia: reparative lineages in the gastrointestinal mucosa. J Pathol. 2018 Jun;245(2):132-137. doi: 10.1002/path.5066.Goldenring J.R. Pyloric metaplasia, pseudopyloric metaplasia, ulcer-associated cell lineage and spasmolytic polypeptide-expressing metaplasia: reparative lineages in the gastrointestinal mucosa. J Pathol. 2018 Jun;245(2):132-137. doi: 10.1002/path.5066.Agoston A.T., Pham T.H., Odze R.D., Wang D.H., Das K.M., Spechler S.J., Souza R.F. Columnar-Lined Esophagus Develops via Wound Repair in a Surgical Model of Reflux Esophagitis. Cell Mol Gastroenterol Hepatol. 2018 Jun 27;6(4):389-404. doi: 10.1016/j.jcmgh.2018.06.007.Agoston A.T., Pham T.H., Odze R.D., Wang D.H., Das K.M., Spechler S.J., Souza R.F. Columnar-Lined Esophagus Develops via Wound Repair in a Surgical Model of Reflux Esophagitis. Cell Mol Gastroenterol Hepatol. 2018 Jun 27;6(4):389-404. doi: 10.1016/j.jcmgh.2018.06.007.Zhang Q., Agoston A.T., Pham T.H. et al. Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett’s Cells. Gastroenterology. 2019 Jan;156(1):130-144.e10. doi: 10.1053/j.gastro.2018.09.046.Zhang Q., Agoston A.T., Pham T.H. et al. Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett’s Cells. Gastroenterology. 2019 Jan;156(1):130-144.e10. doi: 10.1053/j.gastro.2018.09.046.Souza R.F., Huo X., Mittal V. et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009 Nov;137(5):1776-84. doi: 10.1053/j.gastro.2009.07.055.Souza R.F., Huo X., Mittal V. et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009 Nov;137(5):1776-84. doi: 10.1053/j.gastro.2009.07.055.Souza R.F. The role of acid and bile reflux in oesophagitis and Barrett’s metaplasia. Biochem Soc Trans. 2010 Apr;38(2):348-52. doi: 10.1042/BST0380348.Souza R.F. The role of acid and bile reflux in oesophagitis and Barrett’s metaplasia. Biochem Soc Trans. 2010 Apr;38(2):348-52. doi: 10.1042/BST0380348.Souza R.F. From Reflux Esophagitis to Esophageal Adenocarcinoma. Dig Dis. 2016;34(5):483-90. doi: 10.1159/000445225.Souza R.F. From Reflux Esophagitis to Esophageal Adenocarcinoma. Dig Dis. 2016;34(5):483-90. doi: 10.1159/000445225.Souza R.F. Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia. J Gastroenterol. 2017 Jul;52(7):767-776. doi: 10.1007/s00535-017-1342-1.Souza R.F. Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia. J Gastroenterol. 2017 Jul;52(7):767-776. doi: 10.1007/s00535-017-1342-1.Souza R.F., Bayeh L., Spechler S.J., Tambar U.K., Bruick R.K. A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis. Curr Opin Pharmacol. 2017 Dec;37:93-99. doi: 10.1016/j.coph.2017.10.004.Souza R.F., Bayeh L., Spechler S.J., Tambar U.K., Bruick R.K. A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis. Curr Opin Pharmacol. 2017 Dec;37:93-99. doi: 10.1016/j.coph.2017.10.004.Tambunting L., Kelleher D., Duggan S.P. The Immune Underpinnings of Barrett’s-Associated Adenocarcinogenesis: a Retrial of Nefarious Immunologic Co-Conspirators. Cell Mol Gastroenterol Hepatol. 2022;13(5):1297-1315. doi: 10.1016/j.jcmgh.2022.01.023.Tambunting L., Kelleher D., Duggan S.P. The Immune Underpinnings of Barrett’s-Associated Adenocarcinogenesis: a Retrial of Nefarious Immunologic Co-Conspirators. Cell Mol Gastroenterol Hepatol. 2022;13(5):1297-1315. doi: 10.1016/j.jcmgh.2022.01.023.O’Riordan J.M., Abdel-latif M.M., Ravi N. et al. Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Gastroenterol. 2005 Jun;100(6):1257-64. doi: 10.1111/j.1572-0241.2005.41338.x.O’Riordan J.M., Abdel-latif M.M., Ravi N. et al. Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Gastroenterol. 2005 Jun;100(6):1257-64. doi: 10.1111/j.1572-0241.2005.41338.x.Dunbar K.B., Agoston A.T., Odze R.D. et al. Association of Acute Gastroesophageal Reflux Disease With Esophageal Histologic Changes. JAMA. 2016 May 17;315(19):2104-12. doi: 10.1001/jama.2016.5657.Dunbar K.B., Agoston A.T., Odze R.D. et al. Association of Acute Gastroesophageal Reflux Disease With Esophageal Histologic Changes. JAMA. 2016 May 17;315(19):2104-12. doi: 10.1001/jama.2016.5657.Huo X., Agoston A.T., Dunbar K.B. et al. Hypoxia-inducible factor-2α plays a role in mediating oesophagitis in GORD. Gut. 2017 Sep;66(9):1542-1554. doi: 10.1136/gutjnl-2016-312595.Huo X., Agoston A.T., Dunbar K.B. et al. Hypoxia-inducible factor-2α plays a role in mediating oesophagitis in GORD. Gut. 2017 Sep;66(9):1542-1554. doi: 10.1136/gutjnl-2016-312595.Spechler S.J., Merchant J.L., Wang T.C. et al. A Summary of the 2016 James W. Freston Conference of the American Gastroenterological Association: Intestinal Metaplasia in the Esophagus and Stomach: Origins, Differences, Similarities and Significance. Gastroenterology. 2017 Jul;153(1):e6-e13. doi: 10.1053/j.gastro.2017.05.050.Spechler S.J., Merchant J.L., Wang T.C. et al. A Summary of the 2016 James W. Freston Conference of the American Gastroenterological Association: Intestinal Metaplasia in the Esophagus and Stomach: Origins, Differences, Similarities and Significance. Gastroenterology. 2017 Jul;153(1):e6-e13. doi: 10.1053/j.gastro.2017.05.050.Haddad J.J, Harb H.L. Cytokines and the regulation of hypoxia-inducible factor (HIF)-1alpha.Int Immunopharmacol. 2005 Mar;5(3):461-83. doi: 10.1016/j.intimp.2004.11.009.Haddad J.J, Harb H.L. Cytokines and the regulation of hypoxia-inducible factor (HIF)-1alpha.Int Immunopharmacol. 2005 Mar;5(3):461-83. doi: 10.1016/j.intimp.2004.11.009.Hanna S., Rastogi A., Weston A.P., Totta F., Schmitz R., Mathur S., McGregor D., Cherian R., Sharma P. Detection of Barrett’s esophagus after endoscopic healing of erosive esophagitis. Am J Gastroenterol. 2006 Jul;101(7):1416-20. doi: 10.1111/j.1572-0241.2006.00631.x.Hanna S., Rastogi A., Weston A.P., Totta F., Schmitz R., Mathur S., McGregor D., Cherian R., Sharma P. Detection of Barrett’s esophagus after endoscopic healing of erosive esophagitis. Am J Gastroenterol. 2006 Jul;101(7):1416-20. doi: 10.1111/j.1572-0241.2006.00631.x.Modiano N., Gerson L.B. Risk factors for the detection of Barrett’s esophagus in patients with erosive esophagitis. Gastrointest Endosc. 2009 May;69(6):1014-20. doi: 10.1016/j.gie.2008.07.024.Modiano N., Gerson L.B. Risk factors for the detection of Barrett’s esophagus in patients with erosive esophagitis. Gastrointest Endosc. 2009 May;69(6):1014-20. doi: 10.1016/j.gie.2008.07.024.Ronkainen J., Talley N.J., Storskrubb T., Johansson S.E., Lind T., Vieth M., Agréus L., Aro P. Erosive esophagitis is a risk factor for Barrett’s esophagus: a community-based endoscopic follow-up study. Am J Gastroenterol. 2011 Nov;106(11):1946-52. doi: 10.1038/ajg.2011.326.Ronkainen J., Talley N.J., Storskrubb T., Johansson S.E., Lind T., Vieth M., Agréus L., Aro P. Erosive esophagitis is a risk factor for Barrett’s esophagus: a community-based endoscopic follow-up study. Am J Gastroenterol. 2011 Nov;106(11):1946-52. doi: 10.1038/ajg.2011.326.Zampeli E., Karamanolis G., Morfopoulos G. et al. Inflammatory infiltration of metaplastic epithelium and correlation to previous diagnosis of esophagitis and Barrett’s length. Scand J Gastroenterol. 2012 Sep;47(8-9):900-6. doi: 10.3109/00365521.2012.688214.Zampeli E., Karamanolis G., Morfopoulos G. et al. Inflammatory infiltration of metaplastic epithelium and correlation to previous diagnosis of esophagitis and Barrett’s length. Scand J Gastroenterol. 2012 Sep;47(8-9):900-6. doi: 10.3109/00365521.2012.688214.Usui G, Shinozaki T., Jinno T., Fujibayashi K., Morikawa T., Gunji T., Matsuhashi N. Relationship between time-varying status of reflux esophagitis and Helicobacter pylori and progression to long-segment Barrett’s esophagus: time-dependent Cox proportional-hazards analysis. BMC Gastroenterol. 2020 Aug 15;20(1):270. doi: 10.1186/s12876-020-01418-5.Usui G, Shinozaki T., Jinno T., Fujibayashi K., Morikawa T., Gunji T., Matsuhashi N. Relationship between time-varying status of reflux esophagitis and Helicobacter pylori and progression to long-segment Barrett’s esophagus: time-dependent Cox proportional-hazards analysis. BMC Gastroenterol. 2020 Aug 15;20(1):270. doi: 10.1186/s12876-020-01418-5.Peters Y., Honing J., Kievit W., Kestens C., Pestman W., Nagtegaal I.D., van der Post R.S., Siersema P.D. Incidence of Progression of Persistent Nondysplastic Barrett’s Esophagus to Malignancy. Clin Gastroenterol Hepatol. 2019 Apr;17(5):869-877.e5. doi: 10.1016/j.cgh.2018.08.033.Peters Y., Honing J., Kievit W., Kestens C., Pestman W., Nagtegaal I.D., van der Post R.S., Siersema P.D. Incidence of Progression of Persistent Nondysplastic Barrett’s Esophagus to Malignancy. Clin Gastroenterol Hepatol. 2019 Apr;17(5):869-877.e5. doi: 10.1016/j.cgh.2018.08.033.Que J., Garman K.S., Souza R.F., Spechler S.J. Pathogenesis and Cells of Origin of Barrett’s Esophagus. Gastroenterology. 2019 Aug;157(2):349-364.e1. doi: 10.1053/j.gastro.2019.03.072.Que J., Garman K.S., Souza R.F., Spechler S.J. Pathogenesis and Cells of Origin of Barrett’s Esophagus. Gastroenterology. 2019 Aug;157(2):349-364.e1. doi: 10.1053/j.gastro.2019.03.072.Wang D.H., Souza R.F. Transcommitment: Paving the Way to Barrett’s Metaplasia. Adv Exp Med Biol. 2016;908:183-212. doi: 10.1007/978-3-319-41388-4_10.Wang D.H., Souza R.F. Transcommitment: Paving the Way to Barrett’s Metaplasia. Adv Exp Med Biol. 2016;908:183-212. doi: 10.1007/978-3-319-41388-4_10.Zhang W., Wang D.H. Origins of Metaplasia in Barrett’s Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease? Dig Dis Sci. 2018 Aug;63(8):2005-2012. doi: 10.1007/s10620-018-5069-5.Zhang W., Wang D.H. Origins of Metaplasia in Barrett’s Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease? Dig Dis Sci. 2018 Aug;63(8):2005-2012. doi: 10.1007/s10620-018-5069-5.McDonald S.A., Lavery D., Wright N.A., Jansen M. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol. 2015 Jan;12(1):50-60. doi: 10.1038/nrgastro.2014.181.McDonald S.A., Lavery D., Wright N.A., Jansen M. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol. 2015 Jan;12(1):50-60. doi: 10.1038/nrgastro.2014.181.Sawhney R.A., Shields H.M., Allan C.H., Boch J.A., Trier J.S., Antonioli D.A. Morphological characterization of the squamocolumnar junction of the esophagus in patients with and without Barrett’s epithelium. Dig Dis Sci. 1996 Jun;41(6):1088-98. doi: 10.1007/BF02088224.Sawhney R.A., Shields H.M., Allan C.H., Boch J.A., Trier J.S., Antonioli D.A. Morphological characterization of the squamocolumnar junction of the esophagus in patients with and without Barrett’s epithelium. Dig Dis Sci. 1996 Jun;41(6):1088-98. doi: 10.1007/BF02088224.Shields H.M., Zwas F., Antonioli D.A., Doos W.G., Kim S., Spechler S.J. Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett’s epithelium. Dig Dis Sci. 1993 Jan;38(1):97-108. doi: 10.1007/BF01296780.Shields H.M., Zwas F., Antonioli D.A., Doos W.G., Kim S., Spechler S.J. Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett’s epithelium. Dig Dis Sci. 1993 Jan;38(1):97-108. doi: 10.1007/BF01296780.Boch J.A., Shields H.M., Antonioli D.A., Zwas F., Sawhney R.A., Trier J.S. Distribution of cytokeratin markers in Barrett’s specialized columnar epithelium. Gastroenterology. 1997 Mar;112(3):760-5. doi: 10.1053/gast.1997.v112.pm9041237.Boch J.A., Shields H.M., Antonioli D.A., Zwas F., Sawhney R.A., Trier J.S. Distribution of cytokeratin markers in Barrett’s specialized columnar epithelium. Gastroenterology. 1997 Mar;112(3):760-5. doi: 10.1053/gast.1997.v112.pm9041237.Nicholson A.M., Graham T.A., Simpson A. et al. Barrett’s metaplasia glands are clonal, contain multiple stem cells and share a common squamous progenitor. Gut. 2012 Oct;61(10):1380-9. doi: 10.1136/gutjnl-2011-301174.Nicholson A.M., Graham T.A., Simpson A. et al. Barrett’s metaplasia glands are clonal, contain multiple stem cells and share a common squamous progenitor. Gut. 2012 Oct;61(10):1380-9. doi: 10.1136/gutjnl-2011-301174.Reveiller M., Ghatak S., Toia L. et al. Bile exposure inhibits expression of squamous differentiation genes in human esophageal epithelial cells. Ann Surg. 2012 Jun;255(6):1113-20. doi: 10.1097/SLA.0b013e3182512af9.Reveiller M., Ghatak S., Toia L. et al. Bile exposure inhibits expression of squamous differentiation genes in human esophageal epithelial cells. Ann Surg. 2012 Jun;255(6):1113-20. doi: 10.1097/SLA.0b013e3182512af9.Kazumori H., Ishihara S., Rumi M.A., Kadowaki Y., Kinoshita Y. Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium. Gut. 2006 Jan;55(1):16-25. doi: 10.1136/gut.2005.066209.Kazumori H., Ishihara S., Rumi M.A., Kadowaki Y., Kinoshita Y. Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium. Gut. 2006 Jan;55(1):16-25. doi: 10.1136/gut.2005.066209.Huo X., Juergens S., Zhang X. et al. Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett’s epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G278-86. doi: 10.1152/ajpgi.00092.2011.Huo X., Juergens S., Zhang X. et al. Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett’s epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G278-86. doi: 10.1152/ajpgi.00092.2011.Morrow D.J., Avissar N.E., Toia L. et al. Pathogenesis of Barrett’s esophagus: bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells. Surgery. 2009 Oct;146(4):714-21; discussion 721-2. doi: 10.1016/j.surg.2009.06.050.Morrow D.J., Avissar N.E., Toia L. et al. Pathogenesis of Barrett’s esophagus: bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells. Surgery. 2009 Oct;146(4):714-21; discussion 721-2. doi: 10.1016/j.surg.2009.06.050.Tamagawa Y., Ishimura N., Uno G., Yuki T., Kazumori H., Ishihara S., Amano Y., Kinoshita Y. Notch signaling pathway and Cdx2 expression in the development of Barrett’s esophagus. Lab Invest. 2012 Jun;92(6):896-909. doi: 10.1038/labinvest.2012.56.Tamagawa Y., Ishimura N., Uno G., Yuki T., Kazumori H., Ishihara S., Amano Y., Kinoshita Y. Notch signaling pathway and Cdx2 expression in the development of Barrett’s esophagus. Lab Invest. 2012 Jun;92(6):896-909. doi: 10.1038/labinvest.2012.56.Tamagawa Y., Ishimura N., Uno G., Aimi M., Oshima N., Yuki T., Sato S., Ishihara S., Kinoshita Y. Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett’s esophagus. Lab Invest. 2016 Mar;96(3):325-37. doi: 10.1038/labinvest.2015.137.Tamagawa Y., Ishimura N., Uno G., Aimi M., Oshima N., Yuki T., Sato S., Ishihara S., Kinoshita Y. Bile acids induce Delta-like 1 expression via Cdx2-dependent pathway in the development of Barrett’s esophagus. Lab Invest. 2016 Mar;96(3):325-37. doi: 10.1038/labinvest.2015.137.Vega M. E., Giroux V., Natsuizaka M. et al. Inhibition of Notch signaling enhances transdifferentiation of the esophageal squamous epithelium towards a Barrett’s-like metaplasia via KLF4. Cell Cycle. 2014;13(24):3857-66. doi: 10.4161/15384101.2014. 972875.Vega M. E., Giroux V., Natsuizaka M. et al. Inhibition of Notch signaling enhances transdifferentiation of the esophageal squamous epithelium towards a Barrett’s-like metaplasia via KLF4. Cell Cycle. 2014;13(24):3857-66. doi: 10.4161/15384101.2014. 972875.Minacapelli C. D., Bajpai M., Geng X., Cheng C. L., Chouthai A. A., Souza R., Spechler S. J., Das K. M. Barrett’s metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux. Am J Physiol Gastrointest Liver Physiol. 2017 Jun 1;312(6): G615-G622. doi: 10.1152/ajpgi.00268.2016.Minacapelli C. D., Bajpai M., Geng X., Cheng C. L., Chouthai A. A., Souza R., Spechler S. J., Das K. M. Barrett’s metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux. Am J Physiol Gastrointest Liver Physiol. 2017 Jun 1;312(6): G615-G622. doi: 10.1152/ajpgi.00268.2016.Jiang M., Li H., Zhang Y. et al. Transitional basal cells at the squamous-columnar junction generate Barrett’s oesophagus. Nature. 2017 Oct 26;550(7677):529-533. doi: 10.1038/nature24269.Jiang M., Li H., Zhang Y. et al. Transitional basal cells at the squamous-columnar junction generate Barrett’s oesophagus. Nature. 2017 Oct 26;550(7677):529-533. doi: 10.1038/nature24269.Glickman J. N., Chen Y. Y., Wang H. H., Antonioli D. A., Odze R. D. Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett’s esophagus. Am J Surg Pathol. 2001 May;25(5):569-78. doi: 10.1097/00000478-200105000-00002.Glickman J. N., Chen Y. Y., Wang H. H., Antonioli D. A., Odze R. D. Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett’s esophagus. Am J Surg Pathol. 2001 May;25(5):569-78. doi: 10.1097/00000478-200105000-00002.Coad R. A., Woodman A. C., Warner P. J., Barr H., Wright N. A., Shepherd N. A. On the histogenesis of Barrett’s oesophagus and its associated squamous islands: a three-dimensional study of their morphological relationship with native oesophageal gland ducts. J Pathol. 2005 Aug;206(4):388-94. doi: 10.1002/path.1804.Coad R. A., Woodman A. C., Warner P. J., Barr H., Wright N. A., Shepherd N. A. On the histogenesis of Barrett’s oesophagus and its associated squamous islands: a three-dimensional study of their morphological relationship with native oesophageal gland ducts. J Pathol. 2005 Aug;206(4):388-94. doi: 10.1002/path.1804.Krüger L., Gonzalez L. M., Pridgen T. A. et al. Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair. Am J Physiol Gastrointest Liver Physiol. 2017 Sep 1;313(3): G180-G191. doi: 10.1152/ajpgi.00036.2017.Krüger L., Gonzalez L. M., Pridgen T. A. et al. Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair. Am J Physiol Gastrointest Liver Physiol. 2017 Sep 1;313(3): G180-G191. doi: 10.1152/ajpgi.00036.2017.Owen R. P., White M. J., Severson D. T. et al. Single cell RNA-seq reveals profound transcriptional similarity between Barrett’s oesophagus and oesophageal submucosal glands. Nat Commun. 2018 Oct 15;9(1):4261. doi: 10.1038/s41467-018-06796-9.Owen R. P., White M. J., Severson D. T. et al. Single cell RNA-seq reveals profound transcriptional similarity between Barrett’s oesophagus and oesophageal submucosal glands. Nat Commun. 2018 Oct 15;9(1):4261. doi: 10.1038/s41467-018-06796-9.Leedham S. J., Preston S. L., McDonald S. A. et al. Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus. Gut. 2008 Aug;57(8):1041-8. doi: 10.1136/gut.2007.143339.Leedham S. J., Preston S. L., McDonald S. A. et al. Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus. Gut. 2008 Aug;57(8):1041-8. doi: 10.1136/gut.2007.143339.Garman K. S., Kruger L., Thomas S., Swiderska-Syn M., Moser B. K., Diehl A. M., McCall S. J. Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma. Histopathology. 2015 Dec;67(6):771-82. doi: 10.1111/his.12707.Garman K. S., Kruger L., Thomas S., Swiderska-Syn M., Moser B. K., Diehl A. M., McCall S. J. Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma. Histopathology. 2015 Dec;67(6):771-82. doi: 10.1111/his.12707.Schellnegger R., Quante A., Rospleszcz S. et al. Goblet Cell Ratio in Combination with Differentiation and Stem Cell Markers in Barrett Esophagus Allow Distinction of Patients with and without Esophageal Adenocarcinoma. Cancer Prev Res (Phila). 2017 Jan;10(1):55-66. doi: 10.1158/1940-6207.CAPR-16-0117.Schellnegger R., Quante A., Rospleszcz S. et al. Goblet Cell Ratio in Combination with Differentiation and Stem Cell Markers in Barrett Esophagus Allow Distinction of Patients with and without Esophageal Adenocarcinoma. Cancer Prev Res (Phila). 2017 Jan;10(1):55-66. doi: 10.1158/1940-6207.CAPR-16-0117.Becker L., Huang Q., Mashimo H. Lgr5, an intestinal stem cell marker, is abnormally expressed in Barrett’s esophagus and esophageal adenocarcinoma. Dis Esophagus. 2010 Feb;23(2):168-74. doi: 10.1111/j.1442-2050.2009.00979.x.Becker L., Huang Q., Mashimo H. Lgr5, an intestinal stem cell marker, is abnormally expressed in Barrett’s esophagus and esophageal adenocarcinoma. Dis Esophagus. 2010 Feb;23(2):168-74. doi: 10.1111/j.1442-2050.2009.00979.x.von Rahden B. H., Kircher S., Lazariotou M., Reiber C., Stuermer L., Otto C., Germer C. T., Grimm M. LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett’s esophagus? J Exp Clin Cancer Res. 2011 Feb 23;30(1):23. doi: 10.1186/1756-9966-30-23.von Rahden B. H., Kircher S., Lazariotou M., Reiber C., Stuermer L., Otto C., Germer C. T., Grimm M. LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett’s esophagus? J Exp Clin Cancer Res. 2011 Feb 23;30(1):23. doi: 10.1186/1756-9966-30-23.Jang B. G., Lee B. L., Kim W. H.Intestinal Stem Cell Markers in the Intestinal Metaplasia of Stomach and Barrett’s Esophagus. PLoS One. 2015 May 21;10(5): e0127300. doi: 10.1371/journal.pone.0127300.Jang B. G., Lee B. L., Kim W. H.Intestinal Stem Cell Markers in the Intestinal Metaplasia of Stomach and Barrett’s Esophagus. PLoS One. 2015 May 21;10(5): e0127300. doi: 10.1371/journal.pone.0127300.Wang X., Ouyang H., Yamamoto Y. et al. Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell. 2011 Jun 24;145(7):1023-35. doi: 10.1016/j.cell.2011.05.026.Wang X., Ouyang H., Yamamoto Y. et al. Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell. 2011 Jun 24;145(7):1023-35. doi: 10.1016/j.cell.2011.05.026.Xian W., Duleba M., Zhang Y., Yamamoto Y., Ho K. Y., Crum C., McKeon F. The Cellular Origin of Barrett’s Esophagus and Its Stem Cells. Adv Exp Med Biol. 2019;1123:55-69. doi: 10.1007/978-3-030-11096-3_5.Xian W., Duleba M., Zhang Y., Yamamoto Y., Ho K. Y., Crum C., McKeon F. The Cellular Origin of Barrett’s Esophagus and Its Stem Cells. Adv Exp Med Biol. 2019;1123:55-69. doi: 10.1007/978-3-030-11096-3_5.Sarosi G., Brown G., Jaiswal K. et al. Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett’s esophagus. Dis Esophagus. 2008;21(1):43-50. doi: 10.1111/j.1442-2050.2007.00744.x.Sarosi G., Brown G., Jaiswal K. et al. Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett’s esophagus. Dis Esophagus. 2008;21(1):43-50. doi: 10.1111/j.1442-2050.2007.00744.x.Hutchinson L., Stenstrom B., Chen D., Piperdi B., Levey S., Lyle S., Wang T. C., Houghton J. Human Barrett’s adenocarcinoma of the esophagus, associated myofibroblasts, and endothelium can arise from bone marrow-derived cells after allogeneic stem cell transplant. Stem Cells Dev. 2011 Jan;20(1):11-7. doi: 10.1089/scd.2010.0139.Hutchinson L., Stenstrom B., Chen D., Piperdi B., Levey S., Lyle S., Wang T. C., Houghton J. Human Barrett’s adenocarcinoma of the esophagus, associated myofibroblasts, and endothelium can arise from bone marrow-derived cells after allogeneic stem cell transplant. Stem Cells Dev. 2011 Jan;20(1):11-7. doi: 10.1089/scd.2010.0139.Maslyonkina K. S., Konyukova A. K., Alexeeva D. Y., Sinelnikov M. Y., Mikhaleva L. M. Barrett’s esophagus: The pathomorphological and molecular genetic keystones of neoplastic progression. Cancer Med. 2022 Jan;11(2):447-478. doi: 10.1002/cam4.4447.Maslyonkina K. S., Konyukova A. K., Alexeeva D. Y., Sinelnikov M. Y., Mikhaleva L. M. Barrett’s esophagus: The pathomorphological and molecular genetic keystones of neoplastic progression. Cancer Med. 2022 Jan;11(2):447-478. doi: 10.1002/cam4.4447.Naini B. V., Souza R. F., Odze R. D. Barrett’s Esophagus: A Comprehensive and Contemporary Review for Pathologists. Am J Surg Pathol. 2016 May;40(5): e45-66. doi: 10.1097/PAS.0000000000000598.Naini B. V., Souza R. F., Odze R. D. Barrett’s Esophagus: A Comprehensive and Contemporary Review for Pathologists. Am J Surg Pathol. 2016 May;40(5): e45-66. doi: 10.1097/PAS.0000000000000598.Japan Esophageal Society. Japanese Classification of Esophageal Cancer, 11th Edition: part I. Esophagus. 2017;14(1):1-36. doi: 10.1007/s10388-016-0551-7.Japan Esophageal Society. Japanese Classification of Esophageal Cancer, 11th Edition: part I. Esophagus. 2017;14(1):1-36. doi: 10.1007/s10388-016-0551-7.Srivastava A., Odze R. D., Lauwers G. Y., Redston M., Antonioli D. A., Glickman J. N. Morphologic features are useful in distinguishing Barrett esophagus from carditis with intestinal metaplasia. Am J Surg Pathol. 2007 Nov;31(11):1733-41. doi: 10.1097/PAS.0b013e318078ce91.Srivastava A., Odze R. D., Lauwers G. Y., Redston M., Antonioli D. A., Glickman J. N. Morphologic features are useful in distinguishing Barrett esophagus from carditis with intestinal metaplasia. Am J Surg Pathol. 2007 Nov;31(11):1733-41. doi: 10.1097/PAS.0b013e318078ce91.Chandrasoma P. T., Der R., Dalton P., Kobayashi G., Ma Y., Peters J., Demeester T. Distribution and significance of epithelial types in columnar-lined esophagus. Am J Surg Pathol. 2001 Sep;25(9):1188-93. doi: 10.1097/00000478-200109000-00010.Chandrasoma P. T., Der R., Dalton P., Kobayashi G., Ma Y., Peters J., Demeester T. Distribution and significance of epithelial types in columnar-lined esophagus. Am J Surg Pathol. 2001 Sep;25(9):1188-93. doi: 10.1097/00000478-200109000-00010.Srivastava A., Appelman H., Goldsmith J. D., Davison J. M., Hart J., Krasinskas A. M. The Use of Ancillary Stains in the Diagnosis of Barrett Esophagus and Barrett Esophagus-associated Dysplasia: Recommendations From the Rodger C. Haggitt Gastrointestinal Pathology Society. Am J Surg Pathol. 2017 May;41(5): e8-e21. doi: 10.1097/PAS.0000000000000819.Srivastava A., Appelman H., Goldsmith J. D., Davison J. M., Hart J., Krasinskas A. M. The Use of Ancillary Stains in the Diagnosis of Barrett Esophagus and Barrett Esophagus-associated Dysplasia: Recommendations From the Rodger C. Haggitt Gastrointestinal Pathology Society. Am J Surg Pathol. 2017 May;41(5): e8-e21. doi: 10.1097/PAS.0000000000000819.Schlemper R. J., Riddell R. H., Kato Y. et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000 Aug;47(2):251-5. doi: 10.1136/gut.47.2.251.Schlemper R. J., Riddell R. H., Kato Y. et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut. 2000 Aug;47(2):251-5. doi: 10.1136/gut.47.2.251.Reid B. J., Haggitt R. C., Rubin C. E., Roth G., Surawicz C. M., Van Belle G., Lewin K., Weinstein W. M., Antonioli D. A., Goldman H. et al. Observer variation in the diagnosis of dysplasia in Barrett’s esophagus. Hum Pathol. 1988 Feb;19(2):166-78. doi: 10.1016/s0046-8177(88)80344-7.Reid B. J., Haggitt R. C., Rubin C. E., Roth G., Surawicz C. M., Van Belle G., Lewin K., Weinstein W. M., Antonioli D. A., Goldman H. et al. Observer variation in the diagnosis of dysplasia in Barrett’s esophagus. Hum Pathol. 1988 Feb;19(2):166-78. doi: 10.1016/s0046-8177(88)80344-7.Montgomery E., Bronner M. P., Goldblum J. R. et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001 Apr;32(4):368-78. doi: 10.1053/hupa.2001.23510.Montgomery E., Bronner M. P., Goldblum J. R. et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001 Apr;32(4):368-78. doi: 10.1053/hupa.2001.23510.Montgomery E. Update on Grading Dysplasia in Barrett’s Esophagus. Pathology Case Reviews. 2002;7(1):35-42. doi: 10.1097/00132583-200201000-00006Montgomery E. Update on Grading Dysplasia in Barrett’s Esophagus. Pathology Case Reviews. 2002;7(1):35-42. doi: 10.1097/00132583-200201000-00006Duits L. C., Phoa K. N., Curvers W. L. et al. Barrett’s oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel. Gut. 2015;64(5):700-6. doi: 10.1136/gutjnl-2014-307278.Duits L. C., Phoa K. N., Curvers W. L. et al. Barrett’s oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel. Gut. 2015;64(5):700-6. doi: 10.1136/gutjnl-2014-307278.Duits L. C., van der Wel M. J., Cotton C. C. et al. Patients With Barrett’s Esophagus and Confirmed Persistent Low-Grade Dysplasia Are at Increased Risk for Progression to Neoplasia. Gastroenterology. 2017;152(5):993-1001.e1. doi: 10.1053/j.gastro.2016.12.008.Duits L. C., van der Wel M. J., Cotton C. C. et al. Patients With Barrett’s Esophagus and Confirmed Persistent Low-Grade Dysplasia Are at Increased Risk for Progression to Neoplasia. Gastroenterology. 2017;152(5):993-1001.e1. doi: 10.1053/j.gastro.2016.12.008.Kerkhof M., van Dekken H., Steyerberg E. W., Meijer G. A., Mulder A. H., de Bruïne A., Driessen A., ten Kate F. J., Kusters J. G., Kuipers E. J., Siersema P. D.; CYBAR study group. Grading of dysplasia in Barrett’s oesophagus: substantial interobserver variation between general and gastrointestinal pathologists. Histopathology. 2007 Jun;50(7):920-7. doi: 10.1111/j.1365-2559.2007.02706.x.Kerkhof M., van Dekken H., Steyerberg E. W., Meijer G. A., Mulder A. H., de Bruïne A., Driessen A., ten Kate F. J., Kusters J. G., Kuipers E. J., Siersema P. D.; CYBAR study group. Grading of dysplasia in Barrett’s oesophagus: substantial interobserver variation between general and gastrointestinal pathologists. Histopathology. 2007 Jun;50(7):920-7. doi: 10.1111/j.1365-2559.2007.02706.x.Skacel M., Petras R. E., Gramlich T. L., Sigel J. E., Richter J. E., Goldblum J. R. The diagnosis of low-grade dysplasia in Barrett’s esophagus and its implications for disease progression. Am J Gastroenterol. 2000 Dec;95(12):3383-7. doi: 10.1111/j.1572-0241.2000.03348.x.Skacel M., Petras R. E., Gramlich T. L., Sigel J. E., Richter J. E., Goldblum J. R. The diagnosis of low-grade dysplasia in Barrett’s esophagus and its implications for disease progression. Am J Gastroenterol. 2000 Dec;95(12):3383-7. doi: 10.1111/j.1572-0241.2000.03348.x.Fitzgerald R. C., di Pietro M., Ragunath K., Ang Y., Kang J. Y., Watson P., Trudgill N., Patel P., Kaye P. V., Sanders S., O’Donovan M., Bird-Lieberman E., Bhandari P., Jankowski J. A., Attwood S., Parsons S. L., Loft D., Lagergren J., Moayyedi P., Lyratzopoulos G., de Caestecker J.; British Society of Gastroenterology. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014 Jan;63(1):7-42. doi: 10.1136/gutjnl-2013-305372.Fitzgerald R. C., di Pietro M., Ragunath K., Ang Y., Kang J. Y., Watson P., Trudgill N., Patel P., Kaye P. V., Sanders S., O’Donovan M., Bird-Lieberman E., Bhandari P., Jankowski J. A., Attwood S., Parsons S. L., Loft D., Lagergren J., Moayyedi P., Lyratzopoulos G., de Caestecker J.; British Society of Gastroenterology. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014 Jan;63(1):7-42. doi: 10.1136/gutjnl-2013-305372.Weusten B., Bisschops R., Coron E. et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017 Feb;49(2):191-198. doi: 10.1055/s-0042-122140.Weusten B., Bisschops R., Coron E. et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017 Feb;49(2):191-198. doi: 10.1055/s-0042-122140.Reid B. J., Barrett M. T., Galipeau P. C., Sanchez C. A., Neshat K., Cowan D. S., Levine D. S. Barrett’s esophagus: ordering the events that lead to cancer. Eur J Cancer Prev. 1996 Dec;5 Suppl 2:57-65. doi: 10.1097/00008469-199612002-00009.Reid B. J., Barrett M. T., Galipeau P. C., Sanchez C. A., Neshat K., Cowan D. S., Levine D. S. Barrett’s esophagus: ordering the events that lead to cancer. Eur J Cancer Prev. 1996 Dec;5 Suppl 2:57-65. doi: 10.1097/00008469-199612002-00009.Stachler M. D., Camarda N. D., Deitrick C. et al. Detection of Mutations in Barrett’s Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma. Gastroenterology. 2018 Jul;155(1):156-167. doi: 10.1053/j.gastro.2018.03.047.Stachler M. D., Camarda N. D., Deitrick C. et al. Detection of Mutations in Barrett’s Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma. Gastroenterology. 2018 Jul;155(1):156-167. doi: 10.1053/j.gastro.2018.03.047.Caspa Gokulan R., Garcia-Buitrago M. T., Zaika A. I. From genetics to signaling pathways: molecular pathogenesis of esophageal adenocarcinoma. Biochim Biophys Acta Rev Cancer. 2019 Aug;1872(1):37-48. doi: 10.1016/j.bbcan.2019.05.003.Caspa Gokulan R., Garcia-Buitrago M. T., Zaika A. I. From genetics to signaling pathways: molecular pathogenesis of esophageal adenocarcinoma. Biochim Biophys Acta Rev Cancer. 2019 Aug;1872(1):37-48. doi: 10.1016/j.bbcan.2019.05.003.Dulak A. M., Stojanov P., Peng S., Lawrence M. S. et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013 May;45(5):478-86. doi: 10.1038/ng.2591.Dulak A. M., Stojanov P., Peng S., Lawrence M. S. et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013 May;45(5):478-86. doi: 10.1038/ng.2591.Ross-Innes C. S., Becq J., Warren A., Cheetham R. K. et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma. Nat Genet. 2015 Sep;47(9):1038-1046. doi: 10.1038/ng.3357.Ross-Innes C. S., Becq J., Warren A., Cheetham R. K. et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma. Nat Genet. 2015 Sep;47(9):1038-1046. doi: 10.1038/ng.3357.Hamelin R., Fléjou J. F., Muzeau F., Potet F., Laurent-Puig P., Fékété F., Thomas G. TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett’s esophagus. Gastroenterology. 1994 Oct;107(4):1012-8. doi: 10.1016/0016-5085(94)90225-9.Hamelin R., Fléjou J. F., Muzeau F., Potet F., Laurent-Puig P., Fékété F., Thomas G. TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett’s esophagus. Gastroenterology. 1994 Oct;107(4):1012-8. doi: 10.1016/0016-5085(94)90225-9.Davelaar A. L., Calpe S., Lau L. et al. Aberrant TP53 detected by combining immunohistochemistry and DNA-FISH improves Barrett’s esophagus progression prediction: a prospective follow-up study. Genes Chromosomes Cancer. 2015 Feb;54(2):82-90. doi: 10.1002/gcc.22220.Davelaar A. L., Calpe S., Lau L. et al. Aberrant TP53 detected by combining immunohistochemistry and DNA-FISH improves Barrett’s esophagus progression prediction: a prospective follow-up study. Genes Chromosomes Cancer. 2015 Feb;54(2):82-90. doi: 10.1002/gcc.22220.van der Wel M. J., Coleman H. G., Bergman JJGHM, Jansen M., Meijer S. L.; BOLERO working group. Histopathologist features predictive of diagnostic concordance at expert level among a large international sample of pathologists diagnosing Barrett’s dysplasia using digital pathology. Gut. 2020 May;69(5):811-822. doi: 10.1136/gutjnl-2019-318985.van der Wel M. J., Coleman H. G., Bergman JJGHM, Jansen M., Meijer S. L.; BOLERO working group. Histopathologist features predictive of diagnostic concordance at expert level among a large international sample of pathologists diagnosing Barrett’s dysplasia using digital pathology. Gut. 2020 May;69(5):811-822. doi: 10.1136/gutjnl-2019-318985.Kaye P. V., Haider S. A., Ilyas M., James P. D., Soomro I., Faisal W., Catton J., Parsons S. L., Ragunath K. Barrett’s dysplasia and the Vienna classification: reproducibility, prediction of progression and impact of consensus reporting and p53 immunohistochemistry. Histopathology. 2009 May;54(6):699-712. doi: 10.1111/j.1365-2559.2009.03288.x.Kaye P. V., Haider S. A., Ilyas M., James P. D., Soomro I., Faisal W., Catton J., Parsons S. L., Ragunath K. Barrett’s dysplasia and the Vienna classification: reproducibility, prediction of progression and impact of consensus reporting and p53 immunohistochemistry. Histopathology. 2009 May;54(6):699-712. doi: 10.1111/j.1365-2559.2009.03288.x.Kaye P. V., Ilyas M., Soomro I. et al. Dysplasia in Barrett’s oesophagus: p53 immunostaining is more reproducible than haematoxylin and eosin diagnosis and improves overall reliability, while grading is poorly reproducible. Histopathology. 2016 Sep;69(3):431-40. doi: 10.1111/his.12956.Kaye P. V., Ilyas M., Soomro I. et al. Dysplasia in Barrett’s oesophagus: p53 immunostaining is more reproducible than haematoxylin and eosin diagnosis and improves overall reliability, while grading is poorly reproducible. Histopathology. 2016 Sep;69(3):431-40. doi: 10.1111/his.12956.Skacel M., Petras R. E., Rybicki L. A., Gramlich T. L., Richter J. E., Falk G. W., Goldblum J. R. p53 expression in low grade dysplasia in Barrett’s esophagus: correlation with interobserver agreement and disease progression. Am J Gastroenterol. 2002 Oct;97(10):2508-13. doi: 10.1111/j.1572-0241.2002.06032.x.Skacel M., Petras R. E., Rybicki L. A., Gramlich T. L., Richter J. E., Falk G. W., Goldblum J. R. p53 expression in low grade dysplasia in Barrett’s esophagus: correlation with interobserver agreement and disease progression. Am J Gastroenterol. 2002 Oct;97(10):2508-13. doi: 10.1111/j.1572-0241.2002.06032.x.Murray L., Sedo A., Scott M., McManus D., Sloan J. M., Hardie L. J., Forman D., Wild C. P. TP53 and progression from Barrett’s metaplasia to oesophageal adenocarcinoma in a UK population cohort. Gut. 2006 Oct;55(10):1390-7. doi: 10.1136/gut.2005.083295.Murray L., Sedo A., Scott M., McManus D., Sloan J. M., Hardie L. J., Forman D., Wild C. P. TP53 and progression from Barrett’s metaplasia to oesophageal adenocarcinoma in a UK population cohort. Gut. 2006 Oct;55(10):1390-7. doi: 10.1136/gut.2005.083295.Kerkhof M., Steyerberg E. W., Kusters J. G., van Dekken H., van Vuuren A. J., Kuipers E. J., Siersema P. D. Aneuploidy and high expression of p53 and Ki67 is associated with neoplastic progression in Barrett esophagus. Cancer Biomark. 2008;4(1):1-10. doi: 10.3233/cbm-2008-4101.Kerkhof M., Steyerberg E. W., Kusters J. G., van Dekken H., van Vuuren A. J., Kuipers E. J., Siersema P. D. Aneuploidy and high expression of p53 and Ki67 is associated with neoplastic progression in Barrett esophagus. Cancer Biomark. 2008;4(1):1-10. doi: 10.3233/cbm-2008-4101.Sikkema M., Kerkhof M., Steyerberg E. W. et al. Aneuploidy and overexpression of Ki67 and p53 as markers for neoplastic progression in Barrett’s esophagus: a case-control study. Am J Gastroenterol. 2009 Nov;104(11):2673-80. doi: 10.1038/ajg.2009.437.Sikkema M., Kerkhof M., Steyerberg E. W. et al. Aneuploidy and overexpression of Ki67 and p53 as markers for neoplastic progression in Barrett’s esophagus: a case-control study. Am J Gastroenterol. 2009 Nov;104(11):2673-80. doi: 10.1038/ajg.2009.437.Kastelein F., Biermann K., Steyerberg E. W., Verheij J., Kalisvaart M., Looijenga L. H., Stoop H. A., Walter L., Kuipers E. J., Spaander M. C., Bruno M. J.; ProBar-study group. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett’s oesophagus. Gut. 2013 Dec;62(12):1676-83. doi: 10.1136/gutjnl-2012-303594.Kastelein F., Biermann K., Steyerberg E. W., Verheij J., Kalisvaart M., Looijenga L. H., Stoop H. A., Walter L., Kuipers E. J., Spaander M. C., Bruno M. J.; ProBar-study group. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett’s oesophagus. Gut. 2013 Dec;62(12):1676-83. doi: 10.1136/gutjnl-2012-303594.Horvath B., Singh P., Xie H., Thota P. N., Sun X., Liu X. Expression of p53 predicts risk of prevalent and incident advanced neoplasia in patients with Barrett’s esophagus and epithelial changes indefinite for dysplasia. Gastroenterol Rep (Oxf). 2016 Nov;4(4):304-309. doi: 10.1093/gastro/gov045.Horvath B., Singh P., Xie H., Thota P. N., Sun X., Liu X. Expression of p53 predicts risk of prevalent and incident advanced neoplasia in patients with Barrett’s esophagus and epithelial changes indefinite for dysplasia. Gastroenterol Rep (Oxf). 2016 Nov;4(4):304-309. doi: 10.1093/gastro/gov045.Younes M., Brown K., Lauwers G. Y., Ergun G., Meriano F., Schmulen A. C., Barroso A., Ertan A. p53 protein accumulation predicts malignant progression in Barrett’s metaplasia: a prospective study of 275 patients. Histopathology. 2017 Jul;71(1):27-33. doi: 10.1111/his.13193.Younes M., Brown K., Lauwers G. Y., Ergun G., Meriano F., Schmulen A. C., Barroso A., Ertan A. p53 protein accumulation predicts malignant progression in Barrett’s metaplasia: a prospective study of 275 patients. Histopathology. 2017 Jul;71(1):27-33. doi: 10.1111/his.13193.Duits L. C., Lao-Sirieix P., Wolf W. A. et al. A biomarker panel predicts progression of Barrett’s esophagus to esophageal adenocarcinoma. Dis Esophagus. 2019 Jan 1;32(1): doy102. doi: 10.1093/dote/doy102.Duits L. C., Lao-Sirieix P., Wolf W. A. et al. A biomarker panel predicts progression of Barrett’s esophagus to esophageal adenocarcinoma. Dis Esophagus. 2019 Jan 1;32(1): doy102. doi: 10.1093/dote/doy102.Choi Y., Bedford A., Pollack S. The Aberrant Expression of Biomarkers and Risk Prediction for Neoplastic Changes in Barrett’s Esophagus-Dysplasia. Cancers (Basel). 2024 Jun 28;16(13):2386. doi: 10.3390/cancers16132386.Choi Y., Bedford A., Pollack S. The Aberrant Expression of Biomarkers and Risk Prediction for Neoplastic Changes in Barrett’s Esophagus-Dysplasia. Cancers (Basel). 2024 Jun 28;16(13):2386. doi: 10.3390/cancers16132386.Janmaat V. T., van Olphen S. H., Biermann K. E., Looijenga L. H.J., Bruno M. B., Spaander M. C. W. Use of immunohistochemical biomarkers as independent predictor of neoplastic progression in Barrett’s oesophagus surveillance: A systematic review and meta-analysis. PLoS One. 2017 Oct 23;12(10): e0186305. doi: 10.1371/journal.pone.0186305.Janmaat V. T., van Olphen S. H., Biermann K. E., Looijenga L. H.J., Bruno M. B., Spaander M. C. W. Use of immunohistochemical biomarkers as independent predictor of neoplastic progression in Barrett’s oesophagus surveillance: A systematic review and meta-analysis. PLoS One. 2017 Oct 23;12(10): e0186305. doi: 10.1371/journal.pone.0186305.Altaf K., Xiong J. J., la Iglesia D., Hickey L., Kaul A. Meta-analysis of biomarkers predicting risk of malignant progression in Barrett’s oesophagus. Br J Surg. 2017 Apr;104(5):493-502. doi: 10.1002/bjs.10484.Altaf K., Xiong J. J., la Iglesia D., Hickey L., Kaul A. Meta-analysis of biomarkers predicting risk of malignant progression in Barrett’s oesophagus. Br J Surg. 2017 Apr;104(5):493-502. doi: 10.1002/bjs.10484.Snyder P., Dunbar K., Cipher D. J., Souza R. F., Spechler S. J., Konda V. J. A. Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses. Dig Dis Sci. 2019 May;64(5):1089-1097. doi: 10.1007/s10620-019-05586-7.Snyder P., Dunbar K., Cipher D. J., Souza R. F., Spechler S. J., Konda V. J. A. Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses. Dig Dis Sci. 2019 May;64(5):1089-1097. doi: 10.1007/s10620-019-05586-7.

The authors declare that there are no conflicts of interest present.