Methylation Status of E-Cadherin, p14, DAB-Kinase and THBS1 in Non-Specialized Columnar Metaplasia of the Esophagus.
Roberto Herrera-Goepfert, Jose Luis Mosqueda-Vargas, Luis A Herrera, Luis F Onate-Ocana, Clementina Castro-Hernandez, Margarita Camorlinga-Ponce. Instituto Nacional de Cancerología, México, DF, Mexico; Instituto de Investigaciones Biomédicas,UNAM, México, DF, Mexico; Unidad de Investigación Médica de Enfermedades Infecciosas, Centro Médico Nacional Siglo XXI, México, DF, Mexico
Background: Non-specialized columnar metaplasia (gastric metaplasia) of the esophagus is considered as a consequence of gastro-esophageal reflux. Histologically, metaplastic gastric mucosa may display any of those changes commonly observed in normal set gastric mucosa, including Helicobacter pylori infection. In addition to aging, increased methylation of certain genes has been also described in chronic gastritis and in premalignant stages of gastric carcinoma. The aim of this study was to explore the methylation status of E-cadherin (metastasis and invasion), p14 (cell-cycle regulation), DAB-kinase (apoptosis), and THBS1 (angiogenesis) genes, as well as the H. pylori status, in a group of individuals harboring non-specialized columnar metaplasia of the esophagus.
Design: Sixty-eight subjects (33 females and 35 males), with a mean age of 52 years, were included. Distal esophageal mucosa samples obtained by endoscopy and with confirmed histological diagnosis of non-specialized columnar metaplasia (gastric metaplasia) were thoroughly studied, applying the criteria proposed by the Updated Sydney System for Classification and Grading of Gastritis. DNA was also extracted from paraffin blocks and prepared for studying methylation status by the bisulfite modification method, and H. pylori cag A+ status, by PCR.
Results: Helicobacter pylori cag A+ was demonstrated in the esophageal metaplastic mucosa of 18 individuals; the H. pylori cag+ status was significantly associated with hypermethylation of DAB-kinase (p=0.002) and THBS1 (p=0.028) genes. Methylation status of E-cadherin and p14 genes did not show statistically significant differences between H. pylori positive and H. pylori negative cases.
Conclusions: Aberrant CpG methylation occurs in non-specialized columnar metaplasia of the esophagus and is closely related to H. pylori infection. These findings suggest that a subgroup of patients carrying non-specialized columnar metaplasia of the esophagus, could be at a higher risk for developing more severe lesions.
Monday, February 28, 2011 1:00 PM
Poster Session II # 89, Monday Afternoon