Department of Gastroenterology, Jinling Hospital, Nanjing, Jiangsu Province, China.
J Gastroenterol Hepatol. 2012 Oct;27(10):1629-34. doi: 10.1111/j.1440-1746.2012.07219.x.
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.
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).
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.
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.
胃腺瘤（GA）被认为是胃腺癌的癌前病变。Wnt 信号通路在 GA 中的作用很少被确定。本研究旨在确定 Wnt 信号是否在 GA 的发病机制中发挥作用，并阐明 Wnt 信号在 GA 中的作用机制。
本研究比较了 38 例胃腺瘤和腺瘤旁组织（PT）的临床病理特征、幽门螺杆菌（Hp）感染、腺瘤性结肠息肉病（APC）启动子甲基化、APC 和 β-连环蛋白免疫组化表达和突变状态。
PTs、低级别腺瘤（LGA）和高级别腺瘤（HGA）中β-连环蛋白异常表达的比例分别为 0%、9.09%和 81.25%。APC 的免疫反应评分（IRS）在 PTs 中为 5.50±0.5，在 LGA 中为 3.59±1.4，在 HGA 中为 1.8±2.0。LGA 和 HGA 中的评分明显低于 PTs（P=0.000）。IRS 反映了 HGA 中 APC 表达的显著降低（P=0.002）。APC 的缺失表达与β-连环蛋白的表达相关（P=0.000）。4 例 LGA（18.18%）和 9 例 HGA（56.25%）有 APC 启动子甲基化。APC 启动子甲基化与分级（P=0.014）和β-连环蛋白和 APC 的表达相关（P=0.000）。仅在 2 例腺瘤（5.3%）中检测到基因突变。HGA（43.8%）中 Hp 的存在明显高于 LGA（13.6%）（P=0.038）。但与生长模式、大小、APC 过度甲基化和基因突变无统计学相关性。
APC 启动子的高甲基化，而不是涉及 APC 和 β-连环蛋白的突变，可能在 GA 的发展和进展中起作用，导致 Wnt 信号的中度激活。幽门螺杆菌可能会加速胃腺瘤的进展，但发病机制仍需进一步研究。
