title: Dynamics of SOX2 and CDX2 Expression in Barrett's Mucosa.
abstract: Barrett's esophagus (BE) is the replacement of the normal esophageal squamous epithelium by a columnar lining epithelium. It is a premalignant condition for the development of adenocarcinoma of the esophagus and esophagogastric junction. BE is associated with gastroesophageal reflux which might change the expression profile of key transcription factors involved in the establishment of tissue differentiation, namely, SOX2 (associated with esophageal and gastric differentiation) and CDX2 (associated with intestinal differentiation). Here, we sought to characterize the expression profile of SOX2 and CDX2 in the sequential alterations of the esophageal mucosa towards adenocarcinoma and compare it with the well-established gastric and intestinal mucin profiles (MUC5AC, MUC6, and MUC2). We observed that SOX2 and CDX2 expression correlates with gastric and intestinal differentiation in BE, defined by morphological parameters and mucin expression. We show the presence of a complete intestinal profile in BE, without gastric mucins and without SOX2, and we observed an evolutionary modulation of the metaplastic phenotype by SOX2 and CDX2. We observed that adenocarcinomas harbor more frequently a mixed gastric and intestinal phenotype. In conclusion, our study establishes a role for transcription factors SOX2 and CDX2 in the progression from gastric to gastrointestinal differentiation in Barrett's metaplasia.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Barros
authors.affiliation: Portuguese Oncology Institute Francisco Gentil, EPE, Lisbon, Portugal; Beira Interior University, Covilhã, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pereira
authors.affiliation: Portuguese Oncology Institute Francisco Gentil, EPE, Lisbon, Portugal; Beira Interior University, Covilhã, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Callé
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Vânia
authors.initials: V
authors.lastname: Camilo
authors.affiliation: Portuguese Oncology Institute Francisco Gentil, EPE, Lisbon, Portugal.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Cunha
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal; Faculty of Medicine of the University of Porto, Porto, Portugal.
authors.forename: Leonor
authors.identifier: 0000-0003-4207-9258
authors.initials: L
authors.lastname: David
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal; Faculty of Medicine of the University of Porto, Porto, Portugal; Biology Department, Faculty of Sciences of the University of Porto, Porto, Portugal.
authors.forename: Raquel
authors.identifier: 0000-0002-5622-1633
authors.initials: R
authors.lastname: Almeida
authors.affiliation: Portuguese Oncology Institute Francisco Gentil, EPE, Lisbon, Portugal; Beira Interior University, Covilhã, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Dias-Pereira
authors.affiliation: Portuguese Oncology Institute Francisco Gentil, EPE, Lisbon, Portugal; Beira Interior University, Covilhã, Portugal.
authors.forename: Paula
authors.identifier: 0000-0002-0732-2059
authors.initials: P
authors.lastname: Chaves
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D000071616:CDX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000071041:Esophageal Mucosa / Q000378:metabolism* / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D009077:Mucins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors