Distinct TPEF/HPP1 gene methylation patterns in gastric cancer indicate a field effect in gastric carcinogenesis

BackgroundAberrant methylation of the transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene was recently reported in hyperplastic colon polyps, colorectal adenomas and carcinomas. However, there are only limited data on significance of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene methylation in gastric adenocarcinomas.AimThe aim of this study was to determine the prevalence of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 promoter methylation in gastric adenocarcinomas.PatientsStudy population consists of 48 patients with gastric cancer and 11 dyspeptic patients.MethodsUsing the Methylight assay, transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene methylation was assessed in fresh frozen cancer tissue and matched tumoural-free area of patients with gastric cancer and in the gastric mucosa of dyspeptic patients.ResultsTransmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 promoter gene methylation was observed in 35 of 48 (73%) gastric adenocarcinomas, and in 27 of 48 (56%) matched tumoural-free area cases (p = 0.087). In contrast, the occurrence of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 methylation was much lower in gastric mucosa of dyspeptics (1 of 11; 9%) and the difference was significant in comparison with both tumoural tissue (p = 0.0001) and tumoural-free area (p = 0.0047) of cancer patients. Transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene expression was significantly reduced in adenocarcinomas in comparison with matched tumoural-free area (p = 0.022).ConclusionOur data suggest that methylation of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 is present in the majority of gastric adenocarcinomas and in the surrounding tumoural-free area, indicating that this epigenetic change may point to a field effect in the gastric mucosa.