CDX2 expression in the intestinal-type gastric epithelial neoplasia: frequency and significance

CDX2 is an intestinal transcription factor responsible for regulating the proliferation and differentiation of intestinal epithelial cells. In gastric adenocarcinoma, CDX2 expression is known to be associated with limited invasiveness and intestinal phenotypes. The aims of this study were to analyze CDX2 expression in a series of well-characterized cases of gastric epithelial dysplasia, based on the morphologic and mucin phenotypes, and also to analyze CDX2 expression along the metaplasia-dysplasia-carcinoma sequence. CDX2 expression was evaluated in 69 cases of gastric epithelial dysplasia, 88 cases of intestinal-type early gastric cancers, and 56 cases of advanced gastric cancers. Increased CDX2 expression was more frequently associated with adenomatous-type gastric epithelial dysplasia (27/31, 87%) compared with foveolar (7/15, 47%) or hybrid (10/23, 44%) types of gastric epithelial dysplasia ( P = 0.001). CDX2 expression correlated with an increase in CD10 expression ( P = 0.005), and a decrease in MUC5AC expression ( P = 0.001) in gastric epithelial dysplasia. CDX2 expression was also gradually decreased from gastric epithelial dysplasia, to early and advanced gastric cancers ( present in 64, 40 and 27% of the cases, respectively). A negative correlation was also observed between CDX2 expression and the depth of tumor invasion. Our results indicate that CDX2 expression is associated with specific morphological and mucin phenotypes of gastric epithelial dysplasias, and decreases progressively with the advancing stage of gastric cancers, suggesting a possible tumor suppressor role for CDX2. Modern Pathology ( 2010) 23, 54-61; doi: 10.1038/modpathol.2009.135; published online 9 October 2009