Summary
It remains unclear why Barrett's esophagus (BE)-associated adenocarcinoma (EAC) frequently occurs in the 0-3 o'clock area of the BE. The aims of this study were to clarify the localization of specialized intestinal metaplasia (SIM) as a precancerous lesion and of molecular alterations among different locations using four-quadrant biopsies based on the “Seattle” protocol. We prospectively evaluated microsatellite instability, methylation status at the APC, CDKN2A, hMLH1, RUNX3 and MGMT genes, the immunoreactivity of the monoclonal antibody Das-1 for the colonic phenotype, and Ki-67 staining in 10 early EACs and 128 biopsy samples from 32 BE patients. Among the molecular changes, only APC gene hypermethylation was an independent predictive marker of EAC (OR=24.4, p=0.01). SIM was more frequently identified in the 0-3 o'clock quadrant than in the 6-9 o'clock quadrant (p=0.08). The Ki-67 index was higher in SIM than in the columnar-lined epithelium (CLE) without goblet cells (p<0.0001), and in both SIM and CLE with Das-1 reactivity than in those without (p=0.04 and p=0.06, respectively). Furthermore, the index was relatively higher in the 0-3 o'clock quadrant than in the 6-9 o'clock quadrant in cases with Das-1 reactivity. RUNX3 methylation was more frequently found in SIM than in CLE (p=0.04), while the incidence of the other biomarkers did not show a significant difference between the 0-3 o'clock and 6-9 o'clock areas, nor between SIM and CLE. SIM with Das-1 reactivity, but not molecular alterations, in the 0-3 o'clock quadrant may have higher proliferative activity compared to the other areas of the BE.
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