alpha-catenin expression is decreased in human gastric cancers and in the gastric mucosa of first degree relatives

Background and aims-The role of altered cell adhesion is critical for the d evelopment of epithelial cancers. E-cadherin plays an important role in the maintenance of cell-cell adhesion and its function is thought to be regula ted by its associated cytoplasmic proteins, such as alpha-catenin and beta- catenin. To determine the role of alpha-catenin expression in gastric carci nogenesis, we studied its expression in human gastric cancer and in the gas tric mucosa of first degree relatives with no clinical disease. Methods-alpha-Catenin expression was assessed by immunohistochemical analys is and reverse transcriptase-polymerase chain reaction (RT-PCR) using gastr ic tissue specimens from patients with gastric cancer and from the gastric mucosa of first degree relatives of gastric cancer patients and healthy con trols. Results-mRNA levels of alpha-catenin were reduced or absent in 13 of 19 gas tric cancer tissues, which differed significantly from levels found in the tumour free gastric mucosa of cancer patients (p<0.05). Of the cancer sampl es with altered alpha-catenin mRNA levels, alpha-catenin expression was neg ative in seven and decreased in six cases. Interestingly, decreased alpha-c atenin mRNA expression also occurred in the mucosa of the corpus (11/18) an d antrum (4/18) of first degree relatives. In the corpus biopsies alpha-cat enin expression was more often decreased or lost compared with the antrum b iopsies in first degree relatives and healthy controls (p<0.05). Immunohist ochemical analysis revealed membranous expression of alpha-catenin in gastr ic cancer cells and the non-malignant gastric epithelium. However, some can cers also exhibited loss of membranous staining. Generally, loss or downreg ulation of alpha-catenin mRNA in the gastric mucosa was associated with Hel icobacter pylori infection (p<0.05). Conclusion-Our findings suggest that loss or downregulation of alpha-cateni n expression may be an early event in gastric carcinogenesis and may be ass ociated with H pylori infection.