Metaplastic lineages represent critical putative preneoplastic precursors for gastrointestinal
metaplasia. Two metaplastic processes are associated with
gastric cancer: intestinal
metaplasia (the presence of intestinal goblet cell containing lineages in the stomach) and
spasmolytic polypeptide-expressing
metaplasia (SPEM; antralization of the gastric fundus). The
transcription factor Pdx-1 is expressed in the adult pancreatic islet cells as well as the gastric antrum and duodenum. We have previously noted the increase in Pdx-1 expression in models of
TGFalpha overexpression in mice but not in other models of SPEM in rodents. We have therefore sought to examine the presence of Pdx-1 expression in gastric metaplasias and gastric
adenocarcinoma in humans. Tissue microarrays containing
gastric cancers from the fundus and antrum and samples of SPEM and intestinal
metaplasia were immunostained for Pdx-1. Nuclear Pdx-1 expression was observed in only 50% of
antral-derived
cancers and was present in 40% of fundic
tumors. Pdx-1 expression did not correlate with clinical outcome. Although SPEM lineages did not show any staining for Pdx-1, intestinal
metaplasia showed strong nuclear staining for Pdx-1. Thus, Pdx-1 expression is not associated with antralizing
metaplasia (SPEM) but is associated with intestinal
metaplasia. Given the pattern of normal Pdx-1 expression in the duodenum, goblet cell
metaplasia in the stomach may reflect the adoption of a duodenal lineage paradigm.