Z Gastroenterol 2008; 46 - P315
DOI: 10.1055/s-0028-1089690

Methylation of the Estrogen receptor promoter in the development of gastric cancer

M Varbanova 1, J Harder 2, V Engelstaedter 1, H Usadel 1, M Werner 3, HE Blum 2, A zur Hausen 1, OG Opitz 4
  • 1Universitätsklinik Freiburg, Medizin II, Freiburg, Germany
  • 2Universitätsklinik Freiburg, Medizin II, Tumorzentrum Ludwig Heilmeyer, Freiburg, Germany
  • 3Universitätsklinik Freiburg, Institut für Pathologie, Freiburg, Germany
  • 4Universitätsklinik Freiburg, Tumorzentrum Ludwig Heilmeyer, Comprehensive Cancer Center Freiburg, Freiburg, Germany

Introduction: Gastric carcinogenesis is a multistep process including mutation of different genes but also epigenetic events as aberrant promoter methylation leading to gene silencing. Morphologically, disease progression appears as a sequence of intestinal metaplasia-dysplasia-invasive carcinoma, triggered by Helicobacter pylori infection. Methylation of the Estrogen receptor (ER) promoter has been attributed to the development of colorectal cancer and esophageal adenocarcinoma. The role in gastric carcinogenesis remained elusive.

Methods: To study Estrogen receptor promoter methylation by quantitative methylation specific PCR (MSP) we examined gastric mucosa from 49 individuals who underwent an endocopy due to pain of the upper abdomen, from 8 cases with intestinal metaplasia and from 30 individuals with gastric cancer. PCR specimens were analyzed in a blinded fashion and later correlated with histopathological findings.

Results: From the 49 individuals examined, 27 had histologically normal gastric mucosa (13/49) or mild Helicobacter pylori negative gastritis (14/49). Three specimens in this population showed positive MSP results (11%). On the other hand all of the 22 individuals with H. pylori positive gastritis showed ER promoter methylation (100%). Furthermore, the 8 specimens from gastric intestinal metaplasia and 30 samples from gastric cancer tested positive for ER promoter methylation. The correlation of ER promoter methylation with H. pylori gastritis, intestinal metaplasia and gastric carcinoma was highly significant.

Discussion: ER promoter methylation has been reported in the context of esophageal and colon carcinogenesis. Here we show that this epigenetic event is not tumor specific but is also present in risk conditions for the development of gastric cancer i.e. H.p. infection, suggesting that ER promoter methylation might play a role in the early steps of gastric carcinogenesis and possibly can identify individuals at risk for this highly prevalent tumor.