Expression of Pdx-1 in human gastric metaplasia and gastric adenocarcinoma

Charles M. Leys; Sachiyo Nomura; Erin Rudzinski; Michio Kaminishi; Elizabeth Montgomery; Mary Kay Washington; James R. Goldenring

doi:10.1016/j.humpath.2006.04.011

Expression of Pdx-1 in human gastric metaplasia and gastric adenocarcinoma

Charles M. Leys, Sachiyo Nomura, Erin Rudzinski, Michio Kaminishi, Elizabeth Montgomery, Mary Kay Washington, James R. Goldenring

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

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 TGFα 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.

Original language	English (US)
Pages (from-to)	1162-1168
Number of pages	7
Journal	Human pathology
Volume	37
Issue number	9
DOIs	https://doi.org/10.1016/j.humpath.2006.04.011
State	Published - Sep 2006
Externally published	Yes

Keywords

Antrum
Biomarkers
Gastric cancer
Intestinal metaplasia
Pdx-1
SPEM
TFF2

ASJC Scopus subject areas

Pathology and Forensic Medicine

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10.1016/j.humpath.2006.04.011

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@article{ae55ee5921654cd5b2ea8106fcfc66e8,

title = "Expression of Pdx-1 in human gastric metaplasia and gastric adenocarcinoma",

abstract = "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 TGFα 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.",

keywords = "Antrum, Biomarkers, Gastric cancer, Intestinal metaplasia, Pdx-1, SPEM, TFF2",

author = "Leys, {Charles M.} and Sachiyo Nomura and Erin Rudzinski and Michio Kaminishi and Elizabeth Montgomery and Washington, {Mary Kay} and Goldenring, {James R.}",

note = "Funding Information: This study was supported by the following grants: a Department of Veterans Affairs Merit Review Award, a pilot project grant from the Vanderbilt GI Specialized Program of Research Excellence (SPORE) (1P 50 CA95103), the AGA Funderburg Award in Gastric Biology Related to Cancer, Discovery grant from the Vanderbilt-Ingram Cancer Center (to J. R. G.), and a Vanderbilt Clinical Oncology Research Career Development Program Fellowship (K12 CA090625 to C. M. L). ",

year = "2006",

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doi = "10.1016/j.humpath.2006.04.011",

language = "English (US)",

volume = "37",

pages = "1162--1168",

journal = "Human pathology",

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publisher = "W.B. Saunders Ltd",

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T1 - Expression of Pdx-1 in human gastric metaplasia and gastric adenocarcinoma

AU - Leys, Charles M.

AU - Nomura, Sachiyo

AU - Rudzinski, Erin

AU - Kaminishi, Michio

AU - Montgomery, Elizabeth

AU - Washington, Mary Kay

AU - Goldenring, James R.

N1 - Funding Information: This study was supported by the following grants: a Department of Veterans Affairs Merit Review Award, a pilot project grant from the Vanderbilt GI Specialized Program of Research Excellence (SPORE) (1P 50 CA95103), the AGA Funderburg Award in Gastric Biology Related to Cancer, Discovery grant from the Vanderbilt-Ingram Cancer Center (to J. R. G.), and a Vanderbilt Clinical Oncology Research Career Development Program Fellowship (K12 CA090625 to C. M. L).

PY - 2006/9

Y1 - 2006/9

N2 - 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 TGFα 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.

AB - 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 TGFα 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.

KW - Antrum

KW - Biomarkers

KW - Gastric cancer

KW - Intestinal metaplasia

KW - Pdx-1

KW - SPEM

KW - TFF2

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U2 - 10.1016/j.humpath.2006.04.011

DO - 10.1016/j.humpath.2006.04.011

M3 - Article

C2 - 16938521

AN - SCOPUS:33747835620

SN - 0046-8177

VL - 37

SP - 1162

EP - 1168

JO - Human pathology

JF - Human pathology

IS - 9

ER -

Expression of Pdx-1 in human gastric metaplasia and gastric adenocarcinoma

Abstract

Keywords

ASJC Scopus subject areas

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