Upregulation of ornithine decarboxylase mRNA expression in Barrett's esophagus and Barrett's - Associated adenocarcinoma

The Barrett's multistage process is characterized histopathologically by pr ogression from Barrett's intestinal metaplasia to Barrett's esophagus with dysplasia and ultimately adenocarcinoma. Understanding the cellular and mol ecular events in this multistage process may contribute to improved diagnos is and treatment. Ornithine decarboxylase (ODC) is the first enzyme in the biosynthesis of polyamines. Elevated ODC activity has been found to be asso ciated with progression during Barrett's esophagus, but the regulation of O DC gene expression in the development of Barrett's-associated adenocarcinom a has not been reported. The aim of this study was to assess the prevalence and timing of ODC mRNA expression in the Barrett's metaplasia-dysplasia-ad enocarcinoma sequence. ODC mRNA expression levels, relative to the stably e xpressed internal reference gene p-actin, were measured using a quantitativ e reverse transcription-polymerase chain reaction (RT-PCR) method (ABI 7700 Sequence Detector System) in 104 specimens from 19 patients with Barrett's esophagus without carcinoma and 22 patients with Barrett's-associated aden ocarcinoma. The median ODC mRNA expression levels were significantly increa sed in Barrett's esophagus tissues compared to matched normal tissues in pa tients without adenocarcinoma of the esophagus (P = 0.002; Wilcoxon test). A significant progressive increase in ODC mRNA expression was detectable th rough the stages of the metaplasia-dysplasia-carcinoma sequence in patients with Barrett's-associated adenocarcinoma (r = 0.719; P less than or equal to0.001; Spearman's rho test). These findings show that upregulation of ODC mRNA expression is an early event in the development and progression of Ba rrett's-associated adenocarcinoma of the esophagus, and they suggest that h igh ODC mRNA expression levels may be a clinically useful biomarker for the detection of occult adenocarcinoma.