These results indicate that perturbation of the E-cadherin/beta-catenin complex by H. pylori CagA plays an important role in the development of intestinal metaplasia, a premalignant transdifferentiation of gastric epithelial cells from which intestinal-type gastric adenocarcinoma arises.
Because loss of APC, decreased E-cadherin, or abnormal beta-catenin expression did not occur in IM, even when associated with carcinoma these immunostains are unlikely to be of value in the assessment of malignant potential in IM.
In detail, a reduction of both E-cadherin and beta-catenin expression was observed in 8 (67%) out of 12 first-degree relatives and in 6 (67%) out of 9 controls with intestinal metaplasia (p = 0.4).
The cytoplasmic and nuclear accumulation of beta-catenin could be observed in premalignant (atrophic gastritis and intestinal metaplasia) and cancer tissues, particularly in those infiltrated into deep muscular region. beta-catenin mutation was not detected in all of tissue samples with and without translocalized beta-catenin.
CagA also destabilizes the E-cadherin/beta-catenin complex to elicit aberrant activation of the beta-catenin signal that underlies intestinal metaplasia.