Adenomatous and Foveolar Gastric Dysplasia: Distinct Patterns of Mucin Expression and Background Intestinal Metaplasia

Abstract

Gastric epithelial dysplasia (GED) can be morphologically categorized into adenomatous (or intestinal) and foveolar (or gastric) types. Although limited genetic differences have been demonstrated between these subtypes, the expression of various mucins has not been systematically evaluated in this context. Endoscopic mucosal resections from 69 cases of GEDs were evaluated for the expression of MUC2, MUC5AC, MUC6, and CD10. The results were correlated with morphologic categorization and clinicopathologic parameters. GED was classified as adenomatous, foveolar, or hybrid (showing features of both types), on the basis of histologic evaluation. The neighboring intestinal metaplasia (IM) was also evaluated. An adenomatous morphology was seen in 45%, hybrid type in 33.3%, and a “pure” foveolar type was seen in 21.7% of the cases. Foveolar GED was often depressed/flat on endoscopy and showed a statistically significant association with high-grade morphology (P=0.046). Immunohistochemistry confirmed the histologic stratification. The foveolar and hybrid types were more often positive for MUC5AC (P=0.0001 for both) and negative for CD10 (P=0.019 and 0.016, respectively) as compared with adenomatous GED. High-grade morphology was associated with MUC5AC expression regardless of the morphologic phenotype (P=0.026). Foveolar (73.3%) and hybrid (86.9%) GEDs were associated more often with IM showing a retained expression of gastric type mucin than adenomatous GED (29%) (P<0.01 for both). In contrast, adenomatous type (58.1%) of GED was significantly associated with IM showing a complete intestinal phenotype (CD10+) compared with the foveolar (13.3%) and hybrid types (17.4%) of GED (P=0.005 for both comparisons). In conclusion, our study indicates that foveolar and adenomatous types of GED have distinct clinicopathologic features, mucin profiles, and association with different types of IM.