title: Embryonic transcription factors CDX2 and Oct4 are overexpressed in neuroendocrine tumors of the ileum: a pilot study.
abstract: BACKGROUND
  Neuroendocrine tumors (NETs) of the ileum are rare submucosal tumors that are often diagnosed at advanced stages with metastatic spread to the liver causing a carcinoid syndrome. They present as solitary or multiple tumors. In NETs, loss of sequences on chromosomes 11, 16, 18 and 22 or gain of sequences on chromosomes 17 and 19 has been described. In this study we explored the expression of two novel candidate genes, CDX2 and Oct4, in NETs of the ileum and analyzed whether the molecular expression pattern correlates with the clinical phenotype (solitary/multiple tumors).
  
  
  METHODS
  Data from all patients who underwent surgery for a NET of the ileum between 2000 and 2010 were retrieved from a prospective database. For each patient, frozen normal and tumor tissue was used for the comparison of gene expression levels of two putative cancer stem cell markers, CDX2 and Oct4, using real-time PCR (rtPCR). Serial slides from paraffin blocks were used for immunohistochemistry. Gene expression was compared between normal and tumor tissue as well as between solitary and multiple tumors.
  
  
  RESULTS
  78 patients were identified. In rtPCR, a statistically significant higher expression of CDX2 in tumor tissue (p < 0.001) compared to normal tissue was found. The expression of Oct4 was elevated in the tumors, but did not reach the level of significance (p = 0.155). The expression of both candidate genes was confirmed immunohistochemically and showed a nuclear expression pattern. There was no difference in expression between solitary and multiple tumors or between tumors that had already spread to the liver.
  
  
  CONCLUSIONS
  CDX2 is overexpressed in ileum NETs, thus playing a role in the tumorigenesis of these rare tumors. Since expression does not correlate with clinical stage or phenotype, it might be an early event in tumor development.
authors.affiliation: Department of Visceral, Thoracic and Vascular Surgery, Philipp University of Marburg, Marburg, Germany.
authors.forename: A E
authors.initials: AE
authors.lastname: Heverhagen
authors.forename: C
authors.initials: C
authors.lastname: Geis
authors.forename: V
authors.initials: V
authors.lastname: Fendrich
authors.forename: A
authors.initials: A
authors.lastname: Ramaswamy
authors.forename: R
authors.initials: R
authors.lastname: Montalbano
authors.forename: P
authors.initials: P
authors.lastname: Di Fazio
authors.forename: D K
authors.initials: DK
authors.lastname: Bartsch
authors.forename: M
authors.initials: M
authors.lastname: Ocker
authors.forename: K
authors.initials: K
authors.lastname: Quint
mesh_terms: D000328:Adult; D000368:Aged; D000071616:CDX2 Transcription Factor; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007078:Ileal Neoplasms / Q000209:etiology* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000209:etiology* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010865:Pilot Projects; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human