Alteration in the Wnt/β-catenin signaling pathway in gastric neoplasias of fundic gland (chief cell predominant) type

Summary Gastric neoplasia of chief cell–predominant type (GN-CCP) has been reported as a new, rare variant of gastric tumor. GN-CCPs were defined as tumors consisting of irregular anastomosing glands of columnar cells mimicking chief cells of fundic gland with nuclear atypia and prolapse-type submuc...

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Published in:Human pathology 2013-11, Vol.44 (11), p.2438-2448
Main Authors: Hidaka, Yasuhiro, MD, Mitomi, Hiroyuki, MD, PhD, Saito, Tsuyoshi, MD, PhD, Takahashi, Michiko, TBSc, Lee, Se-yong, MD, Matsumoto, Kenshi, MD, Yao, Takashi, MD, PhD, Watanabe, Sumio, MD, PhD
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adenocarcinoma - surgery
Adenoma
Adenomatous Polyposis Coli Protein - genetics
Adenomatous Polyposis Coli Protein - metabolism
Adult
Aged
Aged, 80 and over
APC
AXIN
Axin Protein - genetics
Axin Protein - metabolism
beta Catenin - genetics
beta Catenin - metabolism
Cell Nucleus - genetics
Cell Nucleus - metabolism
Chief Cells, Gastric - metabolism
Chief Cells, Gastric - pathology
DNA Mutational Analysis
Female
Fundic gland/chief cell differentiation
Gastric Mucosa - metabolism
Gastric Mucosa - pathology
Humans
Japan
Male
Middle Aged
Mutation
Neoplasm Recurrence, Local
Pathology
Signal Transduction
Stomach
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Stomach Neoplasms - surgery
Wnt Proteins - genetics
Wnt Proteins - metabolism
Wnt Signaling Pathway
Wnt/β-Catenin
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Summary:Summary Gastric neoplasia of chief cell–predominant type (GN-CCP) has been reported as a new, rare variant of gastric tumor. GN-CCPs were defined as tumors consisting of irregular anastomosing glands of columnar cells mimicking chief cells of fundic gland with nuclear atypia and prolapse-type submucosal involvement. We comparatively evaluated clinicopathologic features between 31 GN-CCPs and 130 cases of conventional gastric adenocarcinoma invading into submucosa (CGA-SM) in additon to nuclear β -catenin immunolabeling and direct sequencing of members of the Wnt/ β -catenin pathway, CTNNB1 , APC , and AXIN , in a subset of these tumors. GN-CCP presented as small protruded lesions located in the upper third of the stomach, with minimal involvement into the submucosa and rare lymphovascular invasion. None of the lesions have demonstrated a recurrence of disease or metastasis on follow-up. Nuclear β -catenin immunolabeling was higher in GN-CCP (labeling index [LI]: median, 19.3%; high expresser [LI >30%], 7/27 cases [26%]) than CGA-SM (median LI, 14.7%; high expresser, 1/19 cases [6%]). Missense mutation of APC was observed in 1 GN-CCP but not CGA-SM. Missense or nonsense mutations of CTNNB1 and AXIN1 were higher in GN-CCPs (14.8%, both) than CGA-SMs (5.3%, both). Missense mutations of AXIN2 were higher in GN-CCPs (25.9%) than in CGA-SMs (10.5%). Overall, 14 (51.9%) of 27 GN-CCPs and 5 (26.3%) of 19 CGA-SM cases harbored at least 1 of these gene mutations. In conclusion, GN-CCPs as a unique variant of nonaggressive tumor are characterized by nuclear β -catenin accumulation and mutation of CTNNB1 or AXIN gene, suggesting activation of the Wnt/ β -catenin pathway.
ISSN:0046-8177
1532-8392
DOI:10.1016/j.humpath.2013.06.002