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Epigenetic regulation of Wnt/β‐catenin signal‐associated genes in gastric neoplasia of the fundic gland (chief cell‐predominant) type
Author(s) -
Murakami Takashi,
Mitomi Hiroyuki,
Yao Takashi,
Saito Tsuyoshi,
Shibuya Tomoyoshi,
Watanabe Sumio
Publication year - 2017
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12509
Subject(s) - axin2 , wnt signaling pathway , methylation , biology , immunostaining , cancer research , catenin , epigenetics , immunohistochemistry , pathology , microbiology and biotechnology , gene , medicine , immunology , genetics
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.