The expression of hepatocyte nuclear factor-4alpha, a developmental regulator of visceral endoderm, correlates with the intestinal phenotype of gastric adenocarcinomas.
OBJECTIVE
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.
Kojima
Kazuhiro
K
Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, Japan.
Kishimoto
Takashi
T
Nagai
Yuichiro
Y
Tanizawa
Tohru
T
Nakatani
Yukio
Y
Miyazaki
Masaru
M
Ishikura
Hiroshi
H
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D004707:Endoderm / Q000502:physiology*; D005753:Gastric Mucosa / Q000196:embryology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000473:pathology*; D010641:Phenotype; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4