Cytoplasmic β‐catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas

Norwood M G A, Bailey N, Nanji M, Gillies R S, Nicholson A, Ubhi S, Darnton J J, Steyn R S, Womack C, Hughes A, Hemingway D, Harrison R, Waters R & Jankowski J A (2010) Histopathology 57, 101–111 Cytoplasmic β-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas Aims:  β-Catenin is an important molecule in cancer biology. Membranous β-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. Methods and 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 β-catenin expression. Increasing β-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 β-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 β-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic β-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 β-catenin could be used as a prognostic marker for less aggressive disease.