title: Differentiation reprogramming in gastric intestinal metaplasia and dysplasia: role of SOX2 and CDX2.
abstract: OBJECTIVE
  Intestinal metaplasia (IM), which results from de-novo expression of CDX2, and dysplasia are precursor lesions of gastric cancer that are associated with an increased risk for cancer development. There is much evidence suggesting a role for the transcription factor SOX2 in gastric differentiation. The aim of this study was to attempt to establish the relationship of SOX2 with CDX2 and with the differentiation reprogramming that characterizes gastric carcinogenesis, to assess their involvement in IM and dysplasia.
  
  
  RESULTS
  Characterization of gastric (SOX2, MUC5AC, and MUC6) and intestinal (CDX2 and MUC2) markers in normal gastric mucosa, in 55 foci of IM and in 26 foci of dysplasia, was performed by immunohistochemistry. SOX2 was expressed in the normal gastric mucosa, in the presumptive stem cell compartment, and was maintained in 7% of the complete (MUC5AC-negative) and 85% of the incomplete (MUC5AC-positive) IM subtypes. Twelve per cent of the dysplastic lesions expressed SOX2, and the association with MUC5AC was lost. CDX2 was present in all IMs and dysplastic lesions.
  
  
  CONCLUSIONS
  SOX2 is associated with gastric differentiation in incomplete IM and is lost in the progression to dysplasia, whereas CDX2 is acquired de novo in IM and maintained in dysplasia. This suggests that the balance between gastric and intestinal differentiation programmes impacts on the gastric carcinogenesis cascade progression.
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.forename: Mónica
authors.initials: M
authors.lastname: Garrido
authors.forename: Pedro
authors.initials: P
authors.lastname: Valente
authors.forename: Sara
authors.initials: S
authors.lastname: Ricardo
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Amaral
authors.forename: Rita
authors.initials: R
authors.lastname: Barros
authors.forename: Paula
authors.initials: P
authors.lastname: Chaves
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Leonor
authors.initials: L
authors.lastname: David
authors.forename: Raquel
authors.initials: R
authors.lastname: Almeida
mesh_terms: D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: CDX2; SOX2; dysplasia; gastric cancer; intestinal metaplasia