title: Intratumoural heterogeneity of intestinal expression reflects environmental induction and progression-related loss of induction in undifferentiated-type gastric carcinomas.
abstract: OBJECTIVE
  Gene expression in tumours is regulated by environmental as well as genetic/epigenetic factors. This study assessed the environmental factors in intestinal expression of gastric cancers.
  
  
  RESULTS
  We immunohistochemically examined intratumoural heterogeneity in the expression of Cdx2, MUC2, MUC5AC and MUC6 in 39 intramucosal and 49 extramucosally invasive undifferentiated-type gastric carcinomas (UGCs), consisting of signet ring cell carcinomas showing a layered structure (LS) in the mucosa and dedifferentiated tubular adenocarcinomas without LS and with minor tubular components (TC). The LS retains mucosal vertical polarity with superficial MUC5AC expression. Loss of this polarity was independent of intestinal expression and associated with extramucosal invasion. In LS(+) UGCs, intestinal expression was enhanced as the size of mucosal spread increased and was significantly reduced with deeper extramucosal invasion, whereas, in LS(-)/TC(+) UGCs, intestinal expression was frequent and predominant in the mucosa and was insignificantly reduced with deeper extramucosal invasion.
  
  
  CONCLUSIONS
  In LS(+) UGCs, intestinal expression showed dynamic alteration probably by environmental induction and progression-related loss of induction, whereas it was relatively stable in LS(-)/TC(+) UGCs. Thus, intestinal expression in UGCs is not useful as a marker of tumour progression because it is also affected by environmental factors and genetic lineage.
authors.affiliation: Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Natsagdorj
authors.forename: H
authors.initials: H
authors.lastname: Sugihara
authors.forename: M
authors.initials: M
authors.lastname: Bamba
authors.forename: T
authors.initials: T
authors.lastname: Hattori
mesh_terms: D000328:Adult; D000368:Aged; D000071616:CDX2 Transcription Factor; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D004777:Environment; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008875:Middle Aged; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D055272:Mucin-6 / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D055272:Mucin-6