Esophageal adenocarcinoma (EAC) is highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. MicroRNAs (miRNAs) are small, non-coding RNAs that function as posttranscriptional regulators of gene expression and were repeatedly proved to play key roles in pathogenesis of BE as well as EAC. In our study, we used Affymetrix GeneChip miRNA arrays to obtain miRNA expression profiles in total of 119 tissue samples [24 normal esophageal mucosa (EM), 60 BE and 35 EAC]. We identified a number of miRNAs, that showed altered expression progressively in sequence EM, BE and EAC, including for instance miR-21, miR-25, miR-194 and miR-196a with increasing levels (P < 0.0015) and miR-203, miR-205, miR-210 and miR-378 with decreasing levels (P < 0.0001). The subsequent analysis revealed four diagnostic miRNA signatures enabling to distinguish EM and BE [12 miRNAs, area under curve (AUC) = 0.971], EM and EAC (13 miRNAs, AUC = 1.0), BE without and BE with dysplasia (21 miRNAs, AUC = 0.856) and BE without dysplastic changes and BE with dysplasia together with EAC (2 miRNAs, AUC = 0.886). We suggest that miRNA expression profiling expands current knowledge in molecular pathology of Barrett's-based carcinogenesis and enables identification of molecular biomarkers for early detection of BE dysplasia and progression to EAC.

BackgroundBarrett's esophagus (BE) is a disease with a rising prevalence in western countries probably due to the unhealthy lifestyle. In significant number of cases it develops to esophageal adenocarcinoma. Two decades ago, important gene regulators (microRNAs) were discovered and their attendance in the process of malignant transformation was demonstrated (e.g. miR-192, 196a, 203). Our aim was to select the patients with the increased risk of malignant transformation before the cancer develops.Methods71 patients with BE disease were selected, slides from FFPE blocks were prepared, the lesions were microdissected and a qPCR relative expression analysis for selected microRNAs (generally known to be connected with malignant transformation process) was carried out.ResultsWe demonstrated unequivocal statistically significant upregulation of two microRNAs (miR-192, 196a) and downregulation of miR-203 and positive miR-196a correlation with progression from intestinal metaplasia to adenocarcinoma compared to normal individuals.ConclusionsWe hypothetize that there do exist changes of selected microRNAs which can undoubtedly distinguish the patients with BE from normal healthy individuals.

Background & Aims: Radiofrequency ablation (RFA) with/without endoscopic resection (ER) is the standard endoscopic treatment modality for Barrett‘s esophagus (BE) related neoplasia (BORN). The main aim of this study was to assess the long-term outcomes of RFA in patients with BORN. Methods: We retrospectively analyzed the prospectively collected data from the Czech national database. Main outcomes were: complete remission of neoplasia (CR-N), complete remission of intestinal metaplasia (CR-IM), recurrence of both neoplasia and IM, and safety. Results: From a total of 170 patients with BORN treated with RFA, 136 patients were analyzed. They were followed up for a median of 27.5 months. Fifty-six patients (41%) had low-grade intraepithelial neoplasia (LGIN), 46 (34%) had high-grade intraepithelial neoplasia (HGIN) and 34 (25%) had early adenocarcinoma (EAC). RFA was combined with previous ER in 65 patients (48%). CR-IM and CR-N were achieved in 77.9% (95% CI 70.0-84.6%) and 98.5% (95% CI 94.8-99.8%). Among 30 patients without CR-IM, 22 (73%) did not have macroscopic signs of BE. Recurrent neoplasia was detected in 4.5% of patients (6/134) and 15% (16/106) experienced a recurrence of IM at the level of the neo-Z-line. Diagnosis of cancer was an independent risk factor for recurrent IM after RFA (OR 7.0, 95% CI 1.6-30.9, p<0.0005). Conclusion: RFA is highly effective in achieving remission in patients with BORN. A significant proportion of patients did not achieve CR-IM or had a recurrence of IM despite macroscopically absent BE. Recurrence of neoplasia was infrequent but not negligible, thus, patients after successful RFA still require endoscopic surveillance.