189 Treatment of Experimental Colitis Using Adenovirus-Directed Expression of Prohibitin

Abstract

associated with an increased risk of neoplastic progression. Aim: To compare the prevalence of DNA promoter hypermethylation in esophageal biopsies of BE patients with residual BE (ND or LGD) after endoscopic ablation therapy versus patients who present with BE and ND or LGD at baseline and have never been treated. Methods: Using a prospective large BE cohort of 220 patients followed over the past 6 years, we performed a case-control study comparing two groups of patients: 1) patients with BE and high-grade dysplasia and/or intramucosal adenocarcinoma who were treated with photodynamic therapy and had residual BE [ND or LGD as the highest grade of dysplasia on follow-up upper endoscopies], and 2) patients with a baseline diagnosis of BE (ND or LGD) who had never undergone endoscopic therapy. All patients had undergone endoscopic surveillance with the Seattle biopsy protocol. Esophageal biopsies of BE from residual disease in group 1 and at baseline in group 2 were analyzed using methylation-specific PCR, and the prevalence of p16 and APC promoter methylation was compared. Results: There were 15 patients with residual BE (ND or LGD) after photodynamic therapy and 82 patients who presented with BE and ND or LGD at baseline and had never been treated. Patients with residual BE (ND or LGD) after ablation had a significantly higher prevalence of DNAmethylation compared to patients who presented with BE and ND or LGD at baseline for both p16 (73% vs. 31%; OR [95% CI]=6.1 [1.7521.2]; p<0.01) and APC (80% vs. 50%; OR [95% CI]=4.0 [1.0-15.3]; p=0.04). Conclusions: Since DNA methylation is a strong predictor of subsequent neoplastic progression to highgrade dysplasia or esophageal adenocarcinoma, the high prevalence of DNA methylation seen in patients with residual BE (ND or LGD) after endoscopic ablation suggest that these patients may have a higher risk of neoplastic progression compared to patients who have an initial presentation of BE and ND or LGD at baseline and have never been treated. Therefore, residual BE (ND or LGD) after endoscopic ablation should likely be managed more aggressively than de novo BE with ND or LGD.