| Research Abstract |
Hepatoid adenocarcinoma (HA) of the stomach consists of the ordinary-type adenocarcinoma, but in addition, it has parts that are composed of hepatocellular carcinoma-like tumor cells. HA also resembles hepatocellular carcinoma in that it has affinity to blood vessels to the extent that grossly visible worm-like tumor thrombi are frequently formed. We have studied the mechanism and clinical significance of the transdifferentiation of gastric carcinoma, by using HA as a model. Using freshly frozen tissues of HA, the hepatocellular phenotype of HA was confirmed by the specific production of mRNA of alpha-fetoprotein and transferrin. In addition, exceedingly increased amounts of albumin mRNA are produced exclusively by HA tissues. Interestingly, HA of the lung was specifically associated with an aberrant expression of a liver-specific transcriptional factor, HNF-4. The loss of heterozygoxity (LOH) at the long arm of chromosome 4 was detected by a microsatellite marler (D4S395), revealing that hepatoid adenocarcinoma has an LOH in common with hepatocellular carcinoma. This indicates that the tumor suppressor gene(s) at 4q locus may be involved in tumor promotion in HA.
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