title: Hypermethylation of adenomatous polyposis coli gene promoter is associated with novel Wnt signaling pathway in gastric adenomas.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Gastroenterology, Jinling Hospital, Nanjing, Jiangsu Province, China.
authors: Zhen-Kai
authors: ZK
authors: Wang
authors: Jiong
authors: J
authors: Liu
authors: Chan
authors: C
authors: Liu
authors: Fang-Yu
authors: FY
authors: Wang
authors: Chun-Yan
authors: CY
authors: Chen
authors: Xin-Hua
authors: XH
authors: Zhang
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000032:analysis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000737:chemistry / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000032:analysis / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D051176:beta Catenin