title: Anterior gradient 2 profiling in Barrett columnar epithelia and adenocarcinoma.
abstract: Barrett esophagus is the precancerous lesion leading to Barrett adenocarcinoma. The natural history of Barrett metaplasia and its neoplastic progression are still controversial. Anterior gradient 2 is up-regulated in both Barrett intestinal metaplasia and Barrett adenocarcinoma, but no information is available on anterior gradient 2 expression in the spectrum of the phenotypic changes occurring in the natural history of Barrett adenocarcinoma (Barrett esophagus cardiac-type metaplasia, Barrett esophagus intestinal metaplasia, low-grade intraepithelial neoplasia [formerly called low-grade dysplasia], and high-grade intraepithelial neoplasia [formerly called high-grade dysplasia]). Applying immunohistochemistry and reverse transcription and quantitative real-time polymerase chain reaction, this study addressed the role of anterior gradient 2 in Barrett carcinogenesis. Anterior gradient 2 expression was assessed semiquantitatively in 125 consecutive biopsy samples in the adenocarcinoma spectrum arising in Barrett esophagus (Barrett esophagus cardiac-type metaplasia, 25; Barrett esophagus intestinal metaplasia, 25; low-grade intraepithelial neoplasia, 25; high-grade intraepithelial neoplasia, 25; Barrett adenocarcinoma, 25). Additional biopsy samples of esophageal squamous mucosa (n=25) served as controls. Anterior gradient 2 messenger RNA expression was also tested (reverse transcription and quantitative real-time polymerase chain reaction) in a different series of 40 samples (esophageal squamous mucosa, 10; Barrett esophagus cardiac-type metaplasia, 10; Barrett esophagus intestinal metaplasia, 10; Barrett adenocarcinoma, 10). Anterior gradient 2 was never expressed in squamous esophageal epithelium but consistently overexpressed (to much the same degree) in the whole spectrum of Barrett disease (Barrett esophagus cardiac-type metaplasia, Barrett esophagus intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and Barrett adenocarcinoma). Anterior gradient 2 messenger RNA was expressed significantly more in Barrett esophagus cardiac-type metaplasia, Barrett esophagus intestinal metaplasia, and Barrett adenocarcinoma than in native squamous epithelium (P<.001), with no significant differences between the 3 groups. Anterior gradient 2 overexpression affects the whole spectrum of the metaplastic/neoplastic lesions involved in Barrett carcinogenesis. This study supports the biological similarity of the nonintestinal and intestinal types of Barrett metaplasia as precursors of Barrett adenocarcinoma.
authors.affiliation: Department of Medical Diagnostic Sciences and Special Therapies, Surgical Pathology and Cytopathology Unit, University of Padova, 35100 Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pizzi
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
authors.forename: Mariangela
authors.initials: M
authors.lastname: Balistreri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Battaglia
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giacometti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zaninotto
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.forename: Michele
authors.initials: M
authors.lastname: De Boni
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D048348:Reverse Transcription
chemical_list: C502296:AGR2 protein, human; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D012333:RNA, Messenger