[The molecular genetic alterations in mucosa of intestines as markers of oncologic progression and estimate of effectiveness of anti-reflux operations in patients with Barrett's esophagus].

The development of disease of Barrett's esophagus is based on processes of metaplasia of epithelium of esophagus when as a result of reflux of gastric juice and bile acids the normal planocellular epithelium of esophagus is replaced by cylindrical epithelium of intestinal type. Thereupon, Barrett's esophagus is progressing up to dysplasia and adenocarcinoma of esophagus. The progression from precancerous states up to tumor is related to development of genome disorders in cells associated with malignant transformation. The genetic and epigenetic alterations conditioning tumor growth can be used as markers of prognosis of clinical course of disease. To receive possible markers of progression of Barrett's esophagus the study was organized concerning methylation of such genes-suppressors of tumor growth as MGMT, CDH1, p16/CDKN2A, DAPK, RAR-β and RUNX3 in patients with Barrett's esophagus and adenocarcinoma of esophagus. The effectiveness of applied anti-reflux surgical treatment was evaluated too. The abnormal methylation of studied genetic panel in patients with Barrett's esophagus prior to surgical treatment was observed reliably more frequently in altered epithelium as compared with unaltered epithelium (p<0.0001), under dysplasia as compared with metaplasia (p<0.0358) and in the presence of long (>3 cm) segments of altered epithelium as compared with short (<3 cm) segments (p=0.0068). In normal epithelium, prior to operation, abnormal methylation of panel of genes was detected in 7/60 (12%) of patients. Against the background of surgical treatment number of long and short segments of altered epithelium of esophagus reliably decreased (p<0.05). At that, in short segments after operation rate of methylation increased significantly (p=0.0068). Though after operation number of patients with Barrett's esophagus and dysplasia and metaplasia decreased, the rate of abnormal methylation in the other patients increased. It is demonstrated that anti-reflux operation ameliorates condition of mucous membrane of esophagus under Barrett's esophagus. However, in cases without regression significant increasing of rate of abnormal methylation of studied panel of genes is occurred. This is a proof that abnormal methylation of system of genes is related to worse response to application of anti-reflux surgical treatment.