Anterior gradient 2 profiling in Barrett columnar epithelia and adenocarcinoma.

I.F. 3.125 - 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