title: Localization of specialized intestinal metaplasia and the molecular alterations in Barrett esophagus in a Japanese population: an analysis of biopsy samples based on the "Seattle" biopsy protocol.
abstract: It remains unclear why Barrett esophagus (BE)-associated adenocarcinoma (EAC) frequently occurs in the 0 to 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 4-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 (odds ratio, 24.4; P = .01). SIM was more frequently identified in the 0 to 3 o'clock quadrant than in the 6 to 9 o'clock quadrant (P = .08). The Ki-67 index was higher in SIM than in the columnar-lined epithelium (CLE) without goblet cells (P < .0001) and in both SIM and CLE with Das-1 reactivity than in those without (P = .04 and P = .06, respectively). Furthermore, the index was relatively higher in the 0 to 3 o'clock quadrant than in the 6 to 9 o'clock quadrant in cases with Das-1 reactivity. RUNX3 methylation was more frequently found in SIM than in CLE (P = .04), whereas the incidence of the other biomarkers did not show a significant difference between the 0 to 3 o'clock and 6 to 9 o'clock areas, nor between SIM and CLE. SIM with Das-1 reactivity, but not molecular alterations, in the 0 to 3 o'clock quadrant may have higher proliferative activity compared to the other areas of the BE.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Fukui
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan. Electronic address: watarij@hyo-med.ac.jp.
authors.forename: Jiro
authors.initials: J
authors.lastname: Watari
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Okugawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kono
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Tozawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Hisatomo
authors.initials: H
authors.lastname: Ikehara
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ohda
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fukui
authors.affiliation: Division of Gastroenterology and Hepatology, Departments of Medicine and Pathology, Robert Wood Johnson Medical School, Rutgers, Cancer Institute of New Jersey, New Brunswick, NJ 08901.
authors.forename: Kiron M
authors.initials: KM
authors.lastname: Das
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D044466:Asian People; D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000473:pathology*; D061346:Laser Capture Microdissection; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000473:pathology; D053842:Microsatellite Instability; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*
keywords: Barrett's esophagus; Columnar-lined epithelium; Das-1; Methylation; Microsatellite instability; Specialized intestinal metaplasia