Molecular findings in Barrett's epithelium.

Barrett's metaplasia is a premalignant condition and remains the number one risk factor for developing adenocarcinoma. The histologic changes leading to adenocarcinoma are accompanied by genetic disturbances of the epithelial cells itself as well as the surrounding stroma. Genetic and epigenetic events affect the cell cycle, leading to growth self-sufficiency and ignoration of antigrowth signals. The balance of cell turnover is instable by avoidance of apoptosis and a general limitless of the replicative potential of the (mutated) stem cells. Sustained angiogenesis, not only a consequence of chronic inflammation, may precede invasion of genetically instable (aneuploid) cells. The principal genetic changes in Barrett's carcinogenesis are comparable to those known from other epithelial malignancies. Loss of p16 gene expression (by deletion or hypermethylation), the loss of p53 expression (by mutation and deletion), the increase in cyclin expression, and the losses of Rb, APC as well as various chromosomal loci have been reported. Since these genetic or epigenetic alterations are neither tumor nor stage specific, they could not gain diagnostic significance as biomarkers until now. Copyright 2004 S. Karger AG, Basel