Molecular Abnormalities in Pediatric Barrett Esophagus: Can We Test for Potential of Neoplastic Progression?

Abstract

Barrett esophagus (BE) is a preneoplastic condition that predisposes to esophageal adenocarcinoma and is a consequence of prolonged gastroesophageal reflux disease. The condition is mainly seen in adults and is thought to be a complex disease in which individual genetic predisposition interacts with environmental stimuli. The aim of our study was to investigate whether genetic biomarkers of potential disease progression are the same in the rare situation of pediatric BE, as described in adults. We performed fluorescence in situ hybridization with probes from Abbott Vysis Corporation on 4-micron sections taken from 48 paraffin-embedded sequential biopsies of 10 cases of BE. The 4 probe sets were specific for HER2 at 17ql2/17 centromere/4 centromere, p16 at 9p21/9 centromere, TP53 at 17pl3/17 centromere/6 centromere, and CCND1 atllql3/11 centromere. The probe sets were validated on 10 cases of adult Barrett adenocarcinoma. Of the 10 cases, 6 biopsies in 5 cases were informative. Two had gain of HER2 detected in 1 biopsy each (1 also had gain of chromosome 17) and 4 separate cases showed p16 deletion in 1 biopsy of each (1 also had gain of chromosome 9). The genetic markers informative in 50% of our cases were also identified in adult patients with Barrett adenocarcinoma. The importance of this study is that even at the pediatric level, BE can show genetic changes associated with neoplastic progression.