title: Down-regulation of claudin-3 is associated with proliferative potential in early gastric cancers.
abstract: BACKGROUND
  Claudins are tight junction (TJ) proteins, and the relationship between the level of expression and localization of TJ protein, and tumor aggressiveness in early gastric cancer (GC) is still far from clear.
  
  
  OBJECTIVE
  To investigate the expression of claudins and Ki-67 in early GC cells and surrounding normal gastric mucosa.
  
  
  METHODS
  A total of 53 early GC lesions removed via endoscopic mucosal resection or endoscopic submucosal resection were evaluated. All of the GCs were characterized as well to moderately differentiated adenocarcinoma. The labeling index (LI) of Ki-67 was calculated for each sample. To assess the prevalence of epithelial TJs, immunofluorescent staining for claudin-3, claudin-4, and claudin-7 was performed. The immunoreactivity was graded according to the percentage of stained cells.
  
  
  RESULTS
  Claudin-3, claudin-4, and claudin-7 expression at TJs in GC and intestinal metaplasia were significantly higher than that in gastric mucosa with no intestinal metaplasia. The Ki-67 LI of GC specimens was inversely correlated with claudin-3 expression, but not with claudin-4 or claudin-7 expression. Claudin-3 expression was significantly lower at the submucosal invasive front of GCs.
  
  
  CONCLUSIONS
  The down-regulation of claudin-3 was associated with the proliferative potential of GC cells, indicating that claudins may have a pivotal role in the progression of GC.
authors.affiliation: Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Okugawa
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Oshima
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Hori
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Tomita
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fukui
authors.forename: Jiro
authors.initials: J
authors.lastname: Watari
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D062465:Claudin-3; D057167:Claudins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D042241:Early Diagnosis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: C568122:CLDN3 protein, human; D062465:Claudin-3; D057167:Claudins; D019394:Ki-67 Antigen; D012333:RNA, Messenger