title: Cytoplasmic beta-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas.
abstract: OBJECTIVE
  beta-Catenin is an important molecule in cancer biology. Membranous beta-catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer.
  
  
  RESULTS
  Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess beta-catenin expression. Increasing beta-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of beta-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer.
  
  
  CONCLUSIONS
  This is one of the largest prognostic studies of beta-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic beta-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic beta-catenin could be used as a prognostic marker for less aggressive disease.
authors.affiliation: Digestive Disease Centre and Department of Surgery, Leicester Royal Infirmary, Leicester, UK.
authors.forename: Michael G A
authors.initials: MG
authors.lastname: Norwood
authors.forename: Neil
authors.initials: N
authors.lastname: Bailey
authors.forename: Manoj
authors.initials: M
authors.lastname: Nanji
authors.forename: Richard S
authors.initials: RS
authors.lastname: Gillies
authors.forename: Anna
authors.initials: A
authors.lastname: Nicholson
authors.forename: Sukh
authors.initials: S
authors.lastname: Ubhi
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Darnton
authors.forename: Richard S
authors.initials: RS
authors.lastname: Steyn
authors.forename: Chris
authors.initials: C
authors.lastname: Womack
authors.forename: Andrew
authors.initials: A
authors.lastname: Hughes
authors.forename: David
authors.initials: D
authors.lastname: Hemingway
authors.forename: Rebecca
authors.initials: R
authors.lastname: Harrison
authors.forename: Rachel
authors.initials: R
authors.lastname: Waters
authors.forename: Janusz A
authors.initials: JA
authors.lastname: Jankowski
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin