Expression of Pdx-1 in human gastric metaplasia and gastric adenocarcinoma.
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.
Leys
Charles M
CM
Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232-2733, USA.
Nomura
Sachiyo
S
Rudzinski
Erin
E
Kaminishi
Michio
M
Montgomery
Elizabeth
E
Washington
Mary Kay
MK
Goldenring
James R
JR
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008679:Metaplasia; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein