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Barrett's esophagus. The significance of p53 in clinical practice
A P Ireland1, G W Clark, T R DeMeester
1Department of Surgery, University of Southern California School of Medicine, Los Angeles 90033-4612, USA.
Objective:
The authors provide an updated review the molecular biology of the p53 tumor suppressor gene with reference to its role in the malignant degeneration of Barrett's esophagus.
Summary Background Data:
Appreciation 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 adenocarcinoma is increasing in frequency in the western world at an alarming rate and is unique because there is a clear metaplasia (Barrett's mucosa)/ dysplasia/carcinoma sequence. p53 malfunction arises as an early event in this carcinogenic process and has been demonstrated in patients with nondysplastic Barrett's metaplasia. The possible causes of p53 malfunction in this setting are discussed. The most reliable method for the detection of p53 mutations is DNA sequencing. p53 immunohistochemistry 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 Barrett's mucosa remains the best clinical predictor of adenocarcinoma. The mutational spectrum observed in these tumors should provide clues to their etiology.