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Mutation spectrum in the Wnt/β-catenin signaling pathway in gastric fundic gland-associated neoplasms/polyps.
- Source :
-
Virchows Archiv : an international journal of pathology [Virchows Arch] 2015 Jul; Vol. 467 (1), pp. 27-38. Date of Electronic Publication: 2015 Mar 29. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Adenomatous Polyps genetics
Aged
Aged, 80 and over
Female
Gastric Fundus pathology
Humans
Immunohistochemistry
Male
Middle Aged
Protein Phosphatase 2 genetics
Stomach Neoplasms genetics
beta Catenin analysis
Adenomatous Polyps pathology
Mutation
Stomach Neoplasms pathology
Wnt Signaling Pathway physiology
beta Catenin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1432-2307
- Volume :
- 467
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Virchows Archiv : an international journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 25820416
- Full Text :
- https://doi.org/10.1007/s00428-015-1753-4