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Hypermethylation of adenomatous polyposis coli gene promoter is associated with novel Wnt signaling pathway in gastric adenomas
Author(s) -
Wang ZhenKai,
Liu Jiong,
Liu Chan,
Wang FangYu,
Chen ChunYan,
Zhang XinHua
Publication year - 2012
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2012.07219.x
Subject(s) - adenomatous polyposis coli , wnt signaling pathway , medicine , methylation , immunohistochemistry , cancer research , dna methylation , adenoma , pathogenesis , catenin , adenocarcinoma , gastroenterology , cancer , pathology , gene expression , signal transduction , colorectal cancer , gene , biology , genetics
Background and Aim: Gastric adenomas (GAs) are considered as premalignant lesions of gastric adenocarcinoma. The role of Wnt signaling pathway in GAs is rarely identified. In the present study, we aimed to determine whether Wnt signaling plays a role in the pathogenesis of GAs, and to clarify the mechanism of Wnt signaling in GAs. Methods: The study investigated the relationship between clinicopathological characteristics, Helicobacter pylori (Hp) infection, adenomatous polyposis coli (APC) promoter methylation, APC and β‐catenin immunohistochemistry expression and mutation status, compared with 38 gastric adenoma and periadenomatous tissues (PTs). Results: The abnormal expression of β‐catenin in PTs, low‐grade adenomas (LGAs) and high‐grade adenomas (HGAs) was 0%, 9.09% and 81.25%. For APC, immunoreactive score (IRS) was 5.50 ± 0.5 in PTs, 3.59 ± 1.4 in LGAs and 1.8 ± 2.0 in HGAs. The scores in LGAs and HGAs were significantly lower than those in PTs ( P = 0.000). IRS reflected significantly reduced expression of APC in HGAs ( P = 0.002). The absent expression of APC had a correlation with the expression of β‐catenin ( P = 0.000). Four LGAs (18.18%) and nine HGAs (56.25%) had methylation of APC. APC promoter methylation correlated with the grade ( P = 0.014) and the expression of β‐catenin and APC ( P = 0.000). Genes mutation was detected in only two adenomas (5.3%). The presence of Hp in HGAs (43.8%) was significantly higher than in LGAs (13.6%) ( P = 0.038). But there was no statistical correlation to growth pattern, size, APC hypermethylation and gene mutation. Conclusion: Hypermethylation of APC promoter, instead of mutations involving APC and β‐catenin, may play a role in the development and progression of GAs contributing to moderate activation of Wnt signaling. Helicobacter pylori may accelerate the progress of gastric adenoma, but the pathogenesis needs further research.