Epidemiology — laboratory: Alterations of E-cadherin, beta-Catenin and FHIT in Gastric Cancer

The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. The FHIT gene is a putative tumour suppressor gene, abnormalities of which may be involved in the gastric carcinogenesis. This study was to analyze the genetic defects of E-cadherin, beta-catenin and Fhit in gastric cancer. We studied the alterations of E-cadherin, beta-catenin and Fhit in a set of 50 primary gastric tumours by using loss of heterozygosity (LOH) analysis, gene mutation screening, detection of aberrant transcripts and immunohistochemistry (IHC). A high frequency of LOH was detected at 16q22.1 containing the E-cadherin locus (75%) and within the FHIT gene (84%). Three cases (6%) showed the identical missense mutation, A592T, in the E-cadherin gene. We found that 7 tumours (18%) had aberrant E-cadherin mRNA in addition to the normal mRNA. Also 34 of 39 (87%) tumours exhibited low FHIT expression or aberrant FHIT mRNA. Reduced expression of E-cadherin, beta-catenin and Fhit was identified at the frequency of 42%, 28% and 78%, respectively. Specially, 11 tumours (22%) exhibited positive cytoplasmic staining for beta-catenin by IHC. Our results support the hypothesis that alterations of E-cadherin, beta-catenin and Fhit play a role in the gastric tumorigenesis.