BARRETTS-ESOPHAGUS - THE SIGNIFICANCE OF P53 IN CLINICAL-PRACTICE

Objective The authors provide an updated review the molecular biology of the p53 tumor suppressor gene with reference to its role in the mal ignant degeneration of Barrett's esophagus. Summary Background Data Ap preciation of the function of the tumor suppressor gene p53 has given new insight into regulation of the cell cycle, and the gene appears to play an important role in many solid tumors, Esophageal adenocarcinom a is increasing in frequency in the western world at an alarming rate and is unique because there is a clear metaplasia (Barrett's mucosa)/d ysplasia/carcinoma sequence. p53 malfunction arises as an early event in this carcinogenic process and has been demonstrated in patients wit h nondysplastic Barrett's metaplasia. The possible causes of p53 malfu nction in this setting are discussed. The most reliable method for the detection of p53 mutations is DNA sequencing. p53 immunohistochemistr y appears too insensitive to act as a reliable marker for the presence of a mutation and cannot be used as a reliable marker for the future development: of cancer. Conclusions High-grade dysplasia within Barret t's mucosa remains the best clinical predictor of adenocarcinoma. The mutational spectrum observed in these tumors should provide clues to t heir etiology.