title: Epigenetic regulation of Wnt/β-catenin signal-associated genes in gastric neoplasia of the fundic gland (chief cell-predominant) type.
abstract: Gastric neoplasia of the fundic gland (chief cell-predominant) type (GNCCP) is a rare variant of gastric tumor. This tumor is associated with activation of the Wnt/β-catenin signaling pathway; however, the mechanisms underlying this activation remain unknown. To elucidate potential roles of Wnt/β-catenin signal-associated gene methylation in GNCCP, we performed β-catenin immunostaining and methylation-specific polymerase chain reaction (PCR) for their associated genes, including SFRPs, APC, AXIN2, and MCC, in 26 GNCCPs [i.e., 11 intramucosal (GNCCP-Ms) and 15 submucosal tumors (GNCCP-SMs)], and compared with 27 fundic gland polyps (FGPs), 12 FGPs with dysplasia (FGP-Ds), 27 conventional gastric adenocarcinomas (CGAs). Nuclear β-catenin labeling indices were higher in GNCCPs and CGAs than in FGPs and FGP-Ds. SFRPs, APC, and AXIN2 were more frequently methylated in GNCCPs and CGAs (SFRP1, 88%/96%; SFRP2, 85%/93%; SFRP4, 73%/81%; APC, 81%/81%; AXIN2, 81%/85%; respectively) than in FGPs and FGP-Ds (37%/50%; 41%/42%; 41%/58%; 37%/33%; 41%/50%; respectively). A significant correlation was seen between nuclear β-catenin expression and methylation of SFRP1 in GNCCPs. Furthermore, nuclear β-catenin expression was significantly frequent in high-methylated GNCCPs than in low-methylated tumors. In conclusion, our results suggest that activation of this pathway, mediated by gene methylation, may be associated with progression of some GNCCP cases, similar to CGAs.
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.|Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Pathology, Japan Labor Health and Welfare Organization, Kanto Rosai Hospital, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Shibuya
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019872:Chief Cells, Gastric / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005748:Gastric Fundus / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D060449:Wnt Signaling Pathway / Q000235:genetics*
keywords: Wnt/β-catenin signaling pathway; epigenetic regulation; fundic gland polyp; gastric adenocarcinoma; gastric neoplasia of chief cell-predominant type