The Expression of Hepatocyte Nuclear Factor-4alpha, a Developmental Regulator of Visceral Endoderm, Correlates with the Intestinal Phenotype of Gastric Adenocarcinomas

Aims: Hepatocyte nuclear factor (HNF)-4alpha 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-4alpha. We investigated the possible involvement of HNF-4alpha 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-4alpha. 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-4alpha expression was exclusively seen in glandular cells with intestinal metaplasia, which was correlated with MUC2 expression (p<0.05) and inversely correlated with MUC5AC expression (p<0.05). All adenocarcinomas more or less expressed HNF-4alpha, with an intense expression being seen in the I-type (p<0.01) and in well-differentiated adenocarcinomas (p<0.03).

Conclusions: HNF-4alpha expression is associated with the intestinal phenotype of non-neoplastic and neoplastic gastric glandular cells, suggesting a possible involvement in the establishment and/or maintenance of the intestinal phenotype of the gastric mucosa and adenocarcinomas.