Reduction in membranous expression of beta-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer

Br J Cancer. 1999 Dec;81(8):1392-7. doi: 10.1038/sj.bjc.6693437.

Abstract

beta-catenin, a component of the E-cadherin-catenin cell adhesion complex, also plays a separate intracellular signalling role, interacting with APC protein. Intracellular accumulation of beta-catenin is common in colorectal neoplasia. beta-catenin abnormalities are associated with poor survival in gastric cancer, but previous studies do not differentiate between membrane-associated and intracellular beta-catenin. In this study we aimed to determine which type of expression abnormalities for E-cadherin, beta-catenin and alpha-catenin correlate with clinico-pathological features and survival in gastric cancer. Immunoperoxidase staining of paraffin-embedded sections from 40 gastric cancers was performed for E-cadherin, alpha- and beta-catenins using microwave unmasking and an avidin-biotin technique. Clinical data were obtained from case records and cancer registry records. Reduced membranous expression of beta-catenin occurred in 10/12 (83%) diffuse and 8/28 (29%) intestinal tumours (P= 0.0014), and was associated with poor differentiation (P= 0.0015) and short survival (P= 0.032), but not with age, sex, tumour size or nodal status. Nuclear expression of beta-catenin was uncommon; cytoplasmic expression was observed in 13/40 cases (33%) but did not correlate with histology, tumour grade or survival. Reduced E-cadherin membrane expression was associated with lymph node metastasis (P= 0.02). Neither E-cadherin or alpha-catenin expression correlated with survival. Reduced membranous expression of beta-catenin predicts poor prognosis in gastric cancer, whilst ectopic intracellular expression is relatively rare. The apparent differences in beta-catenin expression from those found in colon cancer merit further study.

MeSH terms

  • Cadherins / metabolism*
  • Cell Differentiation
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Gastric Mucosa / metabolism
  • Humans
  • Lymphatic Metastasis
  • Prognosis
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survival Analysis
  • Trans-Activators*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin