Sporadic fundic gland polyps: Common gastric polyps arising through activating mutations in the β-catenin gene

Susan C. Abraham, Bunsei Nobukawa, Francis M. Giardiello, Stanley R. Hamilton, Tsung Teh Wu

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Fundic gland polyps (FGPs) are the most common gastric polyps. FGPs traditionally have been regarded as nondysplastic hamartomatous or hyperplastic lesions, but their pathogenesis remains unclear. We have recently shown that somatic adenomatous polyposis coli (APC) gene alterations are frequently present in FGPs associated with familial adenomatous polyposis (FAP), raising the possibility that mutations of the β-catenin gene affecting the APC/β-catenin pathway might be involved in the pathogenesis of sporadic FGPs. We analyzed somatic β-catenin gene mutations in 57 sporadic FGPs from 40 patients without FAP and in 19 FGPs from 13 FAP patients. Direct DNA sequencing of exon 3 encompassing the glycogen synthase kinase-3β phosphorylation region for β-catenin was used with confirmation by HinfI restriction endonuclease digestion. The foveolar epithelium and dilated fundic glands of the polyps were separately microdissected and analyzed in 22 of 57 sporadic FGPs. Activating β-catenin gene mutations were present in 91% (52 of 57) of sporadic FGPs. Both the foveolar epithelium and the dilated fundic gland epithelium comprising the polyps were shown to have the same somatic β-catenin mutation in 21 of 22 (95%) sporadic FGPs. In contrast, β-catenin gene mutations were not present in any of the 19 FAP-associated FGPs (P < 0.000001). The high frequency of β-catenin mutations in sporadic FGPs indicates that these lesions arise through activating mutations of the β-catenin gene. β-catenin mutations in gastrointestinal tract polyps have previously only been demonstrated in a subset of adenomatous (dysplastic) or neoplastic polyps. Sporadic FGPs are therefore the only lesions of the gastrointestinal tract to demonstrate β-catenin mutations while lacking dysplastic morphology.

Original languageEnglish (US)
Pages (from-to)1005-1010
Number of pages6
JournalAmerican Journal of Pathology
Volume158
Issue number3
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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