Molecular biology of Barrett's adenocarcinoma

Objective To review the current knowledge on the genetic alterations involv ed in the development and progression of Barrett's esophagus-associated neo plastic lesions. Summary Background Data Barrett's esophagus (BE) is a premalignant conditio n in which the normal squamous epithelium of the esophagus is replaced by m etaplastic columnar epithelium. BE predisposes patients to the development of esophageal adenocarcinoma. Endoscopic surveillance can detect esophageal adenocarcinomas when they are early and curable, but most of the adenocarc inomas are detected at an advanced stage. Despite advances in multimodal th erapy, the prognosis for invasive esophageal adenocarcinoma is poor. A bett er understanding of the molecular evolution of the Barrett's metaplasia to dysplasia to adenocarcinoma sequence may allow improved diagnosis, therapy, and prognosis. Methods The authors reviewed data from the published literature to address what is known about the molecular changes thought to be important in the pa thogenesis of BE-associated neoplastic lesions. Results The progression of Barrett's metaplasia to adenocarcinoma is associ ated with several changes in gene structure, gene expression, and protein s tructure. Some of the molecular alterations already showed promise as marke rs for early cancer detection or prognostication. Among these, alterations in the p53 and p16 genes and cell cycle abnormalities or aneuploidy appear to be the most important and well-characterized molecular changes. However, the exact sequence of events is not known, and probably multiple molecular pathways interact and are involved in the progression of BE to adenocarcin oma. Conclusions Further research into the molecular biology of BE-associated ad enocarcinoma will enhance our understanding of the genetic events critical for the initiation and progression of Barrett's adenocarcinoma, leading to more effective surveillance and treatment.