Mutation spectrum in the Wnt/β-catenin signaling pathway in gastric fundic gland-associated neoplasms/polyps

Frequent activation of the Wnt/β-catenin signaling pathway has recently been demonstrated in gastric adenocarcinoma/neoplasia of chief cell predominant type (GA-CCP/GN-CCP) with submucosal involvement. In this study, we examined the activation status of the Wnt/β-catenin signaling pathway in GN-CCP...

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Bibliographic Details
Published in:Virchows Archiv : an international journal of pathology 2015-07, Vol.467 (1), p.27-38
Main Authors: Lee, Se-Yong, Saito, Tsuyoshi, Mitomi, Hiroyuki, Hidaka, Yasuhiro, Murakami, Takashi, Nomura, Ryosuke, Watanabe, Sumio, Yao, Takashi
Format: Article
Language:English
Subjects:
Adenomatous Polyps - genetics
Adenomatous Polyps - pathology
Aged
Aged, 80 and over
beta Catenin - analysis
beta Catenin - genetics
Female
Gastric Fundus - pathology
Humans
Immunohistochemistry
Male
Medicine
Medicine & Public Health
Middle Aged
Mutation
Original Article
Pathology
Protein Phosphatase 2 - genetics
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Wnt Signaling Pathway - physiology
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Summary:Frequent activation of the Wnt/β-catenin signaling pathway has recently been demonstrated in gastric adenocarcinoma/neoplasia of chief cell predominant type (GA-CCP/GN-CCP) with submucosal involvement. In this study, we examined the activation status of the Wnt/β-catenin signaling pathway in GN-CCP without submucosal involvement, which is referred to as gastric dysplasia-CCP (GD-CCP). We also examined β-catenin expression and the mutation spectrum of PPP2R1A and Wnt pathway genes in 11 cases of GD-CCP, 25 cases of gastric polyps of fundic gland type (GPs-FG), and 21 cases of GPs-FG with dysplasia (GP-FGD). β-catenin nuclear staining was observed in 3 cases of GD-CCP, none of GPs-FG, and 6 cases of GPs-FGD. Mutations in Wnt pathway genes, including PPP2R1A , were observed in 4 cases of GDs-CCP, 10 cases of GPs-FG, and 7 cases of GPs-FGD. Two of these seven GPs-FGD cases showed β-catenin nuclear staining. However, none of the 4 GD-CCP cases with mutations or the 10 GPs-FG cases with mutations showed β-catenin nuclear staining. PPP2R1A mutations were observed in 1 GD-CCP case and 1 GPs-FGD case. Although the mutation spectra of the Wnt pathway genes in GD-CCP and GP-FG differed, based on the absence of β-catenin nuclear staining despite the genetic alterations, GD-CCP is more similar to GP-FG than to GN-CCP, which shows β-catenin nuclear staining and submucosal involvement. Activation of the Wnt/β-catenin signaling by the β-catenin nuclear transition may be required during progression from GD-CCP to GN-CCP. Furthermore, this is the first report describing PPP2R1A mutations in gastric fundic gland-associated neoplasms.
ISSN:0945-6317
1432-2307
DOI:10.1007/s00428-015-1753-4