P53 IMMUNOREACTIVITY IN BARRETTS METAPLASIA, DYSPLASIA, AND CARCINOMA

Barrett's esophagus is a metaplastic condition with an unpredictable p otential for neoplasia. Mutations of the tumor-suppressor gene p53 hav e been implicated in the evolution of some carcinomas. These mutations frequently result in intranuclear protein accumulation, which can be detected immunohistochemically. This study was undertaken to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of ne oplasia and, if so, when it occurs in the metaplasia-dysplasia-carcino ma sequence. Twenty-eight esophageal resection specimens were studied. Barrett's mucosa was present in each specimen, low-grade dysplasia in 27, high-grade dysplasia in 26, intramucosal cancer in 18, and submuc osal cancer in 5. Immunohistochemical staining with the monoclonal ant ibody Pab1801 was used to detect the intranuclear protein product of m utated p53. No p53 immunoreactivity was seen in specimens of Barrett's mucosa or low-grade dysplasia. p53 immunoreactivity was found only in specimens of high-grade dysplasia, intramucosal cancer and submucosal cancer. Sixty-nine percent (18/26) of these specimens exhibited mutat ed p53; 18 of 26 specimens of high-grade dysplasia (69%), 12 of 18 int ramucosal cancer specimens (67%), and two of five submucosal cancer sp ecimens (40%) expressed mutated p53. When p53 staining was observed, t he spectrum of neoplastic changes (high-grade dysplasia, intramucosal cancer, submucosal cancer) within the specimen was positive. We conclu de that (1) p53 immunoreactivity in Barrett's esophagus is a frequent, but not inclusive, marker for high-grade dysplasia, intramucosal canc er and (2) immunoreactivity occurs late in the metaplasia-dysplasia-ca rcinoma sequence, during the transition to high-grade dysplasia.