title: Epithelial-mesenchymal transition markers in the differential diagnosis of gastroenteropancreatic neuroendocrine tumors.
abstract: OBJECTIVE
  To elucidate the role of epithelial-mesenchymal transition markers in gastroenteropancreatic neuroendocrine tumors (GEP NETs) and the potential usefulness in their clinical management.
  
  
  METHODS
  One hundred ten GEP NET paraffin-embedded samples were immunohistochemically analyzed for E-cadherin, N-cadherin, β-catenin, vimentin, Snail1, Snail2, Twist, and Foxc2 protein expression.
  
  
  RESULTS
  The 5-year survival rate was reduced for those patients showing high Snail1 protein levels, a cytoplasmic E-cadherin pattern, reduced N-cadherin expression, and loss of E-cadherin/β-catenin adhesion complex integrity at the cell membrane. Interestingly, high β-catenin expression was useful in identifying a grade 1 NET subgroup with a favorable clinical course. Importantly, it also helped to discriminate small-cell vs large-cell grade 3 neuroendocrine carcinomas.
  
  
  CONCLUSIONS
  β-Catenin and N-cadherin immunohistochemical detection might be a useful tool in the differential diagnosis of small-cell vs large-cell G3 neuroendocrine carcinomas. High Snail1 and Foxc2 expression is associated with the invasion and metastatic spread of GEP NETs.
authors.affiliation: Laboratorio del Banco de Tumores-Anatomia Patológica, c/ Celestino Villamil, s/n, 33006 Oviedo, Spain. galvanjose@uniovi.es
authors.forename: Jose A
authors.initials: JA
authors.lastname: Galván
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: Aitana
authors.initials: A
authors.lastname: Vallina
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Fonseca
authors.forename: Lourdes
authors.initials: L
authors.lastname: Gómez-Izquierdo
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Carbonero
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: González
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D003937:Diagnosis, Differential; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D013030:Spain; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D051858:Forkhead Transcription Factors; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; C082078:mesenchyme fork head 1 protein
keywords: E-cadherin; EMT; Foxc2; Neuroendocrine tumors; Snail1; Snail2; β-catenin