Hepatoid adenocarcinoma of the stomach: histogenesis and progression in association with intestinal phenotype.

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. The lesions contain a tubular adenocarcinoma that seems to develop "hepatoid" features, but the relation between the tubular adenocarcinomatous and the hepatoid components remains unclear. We compared the cellular phenotypes of 23 cases of hepatoid adenocarcinoma of the stomach having tubular adenocarcinomatous components with 69 cases of non-hepatoid adenocarcinoma of the stomach. Afterward, we examined the expression of CDX2 and p53 in the tubular adenocarcinomatous and hepatoid components of hepatoid adenocarcinoma. Both components of hepatoid adenocarcinoma were classified into 4 phenotypic categories according to the immunohistochemical results for CD10, MUC2, MUC5AC, and MUC6. The complete intestinal phenotype (CD10+, MUC5AC-, MUC6-) was most frequently observed in the adenocarcinomatous and hepatoid components (61% and 65%, respectively). In contrast, no gastric phenotype (MUC5AC+, MUC6+, MUC2-, CD10-) was observed in any of the hepatoid adenocarcinoma components. The positivity for p53 protein in the adenocarcinomatous and hepatoid components was concordant. The expression of CDX2 with early differentiation and maintenance of intestinal epithelial cells was observed in all of the adenocarcinomatous components, whereas 9 of the 23 hepatoid components (39%) were negative for CDX2. These findings suggest that hepatoid adenocarcinoma arises from an adenocarcinoma with an intestinal phenotype and that its hepatoid component is in some way related to reduced CDX2 expression.