198 CpG-Island Methylator Phenotype (CIMP) and Alterations in RAS-Raf Signaling in Hereditary Non-Polyposis Colorectal Cancers Without Mismatch Repair Deficiency (MSS HNPCC)

control study of eight methylation biomarkers in BE. Progressors (Ps) were defined as BE patients with index biopsies showing no dysplasia, indefinite for dysplasia, or low-grade dysplasia (LGD) at endoscopy performed ≥6 months prior to a diagnosis of either highgrade dysplasia or EAC. Nonprogressors (NPs) were defined as patients undergoing at least 3 surveillance endoscopic examinations who never progressed beyond LGD. Ps were considered as a single combined group and in two tiers: progression within 2 years or 4 years. Methylation was assessed in 145 NPs and 50 Ps using real-time quantitative methylation-specific PCR. RESULTS: Ps were significantly older than NPs (70.6 vs. 62.5 years, p < 0.001). Normalized methylation values of HPP1, p16 and RUNX3 were significantly higher in Ps than in NPs (0.456, 0.138, and 0.104 vs. 0.273, 0.069 and 0.063; p = 0.0025, 0.0066 and 0.0002, respectively). We also evaluated a linear combination of the 8 markers using coefficients from a multivariate logistic regression analysis. Based on this model, areas under the ROC curve (AUCs) were high in the 2-year, 4-year and combined models (0.843, 0.829 and 0.840; p