Barrett's esophagus: model of neoplastic progression.

Human cancer progression is characterized by clonal expansion of cells with accumulated genetic errors. Invasive carcinomas contain all the genetic errors that were acquired during neoplastic progression and then continue to accumulate further abnormalities, leading to tumor heterogeneity. Many investigations of human cancer have given valuable insights in genetic abnormalities important for tumor biology. Early events responsible for neoplastic progression, however, are often impossible to investigate in invasive cancers because the premalignant tissue in which the tumors develop are often overgrown and the premalignant conditions cannot be studied in vivo because they are either not detected owing to lack of symptoms or are removed before cancer develops. Unlike many other premalignant conditions Barrett's esophagus is often associated with symptoms leading to diagnosis at an early stage before cancer develops, and the premalignant epithelium is seldom removed at an early stage of cancer progression. Furthermore, in patients who present with invasive carcinoma the tumor is often surrounded by premalignant epithelium, which is available for further investigations. Therefore Barrett's esophagus is an excellent model in which to study the early events of neoplastic progression. It may not only contribute to a better understanding of the neoplastic process but also provide a base for safer assessment of cancer risk during surveillance for early detection of esophageal adenocarcinoma.