title: Cluster analysis of claudin-1 and -4, E-cadherin, and β-catenin expression in colorectal cancers.
abstract: OBJECTIVE
  Intercellular adhesion mediated by the claudin and cadherin/catenin complex is a prerequisite for epithelial integrity and differentiation, and has been suggested to be frequently disturbed in cancers. The aim of this study was to assess the relationship between such abnormality and clinicopathological features of colorectal carcinomas.
  
  
  METHODS
  Immunohistochemical analysis of claudin-1 and -4, E-cadherin, and β-catenin was performed on a series of 156 cases.
  
  
  RESULTS
  Significant positive associations (P < 0.05-0.001) were found with immunoreactivity for each except nuclear β-catenin. Reduced expression was correlated with poor tumor differentiation (claudin-1, P = 0.035; claudin-4, P = 0.011; E-cadherin, P < 0.001; membranous β-catenin, P = 0.002), an advanced TNM stage (claudin-1, P = 0.002; claudin-4, P = 0.008), and a poor prognosis. On multivariate analysis, reduced expression of E-cadherin (P < 0.001) and β-catenin (P = 0.048) at invasive fronts proved to be an independent predictor of short survival. Hierarchical cluster analysis identified three distinct groups with a good, intermediate, and poor prognosis, having an independent survival outcome by multivariate analysis (good or intermediate vs. poor: hazard ratio, 2.66; 95% confidence interval, 1.54-4.60; P < 0.001).
  
  
  CONCLUSIONS
  Disruption of cell adhesion molecules correlates with tumor differentiation and progression in colorectal carcinomas. Specific marker profiles were identified here as independent prognostic indicators.
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
authors.forename: Hideki
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Takuo
authors.initials: T
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D017024:Chemotherapy, Adjuvant; D062445:Claudin-1; D062506:Claudin-4; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; C568157:CLDN4 protein, human; D015820:Cadherins; D062445:Claudin-1; D062506:Claudin-4; D008565:Membrane Proteins; D051176:beta Catenin