Genetic alterations in Barrett's esophagus and esophageal adenocarcinoma

Barrett's esophagus and esophageal adenocarcinoma are increasing health problems in the Western world. The rise in incidence of esophageal adenocarcinoma is greater than that for any other malignancy in Caucasian populations. The social impact of the disease is stressed in addition by the very aggressive nature of esophageal adenocarcinomas with 5-year survival rates of less than 25%. Far more people develop the premalignant condition Barrett's metaplasia than high grade dysplasia and invasive carcinoma. This means that fortunately not all patients with Barrett's metaplasia will make the progression to high grade disease. It is hoped that by unravelling the molecular mechanisms involved in the neoplastic transformation in Barrett's esophagus it will become possible to predict disease progression in the individual patient. This would be a major step forward in the curative treatment of this disease. In addition, identification of the crucial molecular pathways involved in esophageal adenocarcinogenesis would facilitate the development of new treatment strategies. The molecular mechanisms underlying the initiation and progression of this disease are largely unknown. In this review the histological sequence of Barrett's metaplasia via dysplasia to adenocarcinoma is introduced; then the general molecular concepts of carcinogenesis are explained. Furthermore, the most important esophageal neoplasia related genes are described including their possible role in the neoplastic process. The frequent genomic aberrations are put in relation to the different histological entities. Finally, as future prospect, a molecular grading of esophageal adenocarcinogenesis is anticipated.