The expression of hepatocyte nuclear factor-4α, a developmental regulator of visceral endoderm, correlates with the intestinal phenotype of gastric adenocarcinomas

Aims: Hepatocyte nuclear factor (HNF)‐4α is a developmental regulator of the visceral endoderm, which is expressed in the embryonic gut and later in the adult intestine and colon. However, adult gastric mucosa does not express HNF‐4α. We investigated the possible involvement of HNF‐4α in intestinal metaplasia and the intestinalisation of gastric adenocarcinomas.Methods: Thirty‐five cases of adenocarcinomas and 46 cases of adjacent non‐neoplastic mucosa with (22 lesions) or without (24 lesions) intestinal metaplasia were immunostained for HNF‐4α. The gastric or the intestinal phenotype was also examined using immunohistochemistry for MUC5AC, MUC2, CD10, and gastric‐type mucin (GTM). Adenocarcinomas were classified into the gastric type (G‐type, 42.9%), the mixed gastric and intestinal type (GI‐type, 31.4%), and the intestinal type (I‐type, 25.7%).Results: The HNF‐4α expression was exclusively seen in glandular cells with intestinal metaplasia, which was correlated with MUC2 expression (p<0.05) and inversel...