Expression of p53, PCNA, and C-erbB-2 in Barrett's Metaplasia and Adenocarcinoma

We sought to determine if an immunohistochemicalpanel of p53, PCNA, and c-erbB-2 was a useful biomarkerof transformation in Barrett's metaplasia. P53, PCNA,and c-erbB-2 immunohistochemistry was performed on resected Barrett's specimens selected toshow discrete grades of dysplasia and then onprospectively obtained biopsies. In resection specimens,p53 was positive in 36% with no dysplasia, in 30% with low-grade dysplasia, in 85% with high-gradedysplasia, and in 90% of adenocarcinomas. While anevaluation of proliferation throughout the specimen didnot differ between groups, surface proliferation was significantly higher in high-grade dysplasiathan in low-grade or no dysplasia. All high-gradedysplasia specimens were positive for at least onemarker, compared to 44% with no or low-grade dysplasia. C-erbB-2 was only seen in 31% with high-gradedysplasia and in 10% of adenocarcinomas. Prospectively,the panel had a sensitivity of 100%, a specificity of81% and an overall accuracy of 83% in identifying patients who developed high-grade dysplasia orcancer. Thus, overexpression of p53 occurs early in themalignant transformation of Barrett's and increases withhistologic progression, and proliferation at the surface of Barrett's epitheliumincreases with progressive grades of dysplasia. Animmunohistochemical panel of p53 and PCNA is a usefulbiomarker for Barrett's metaplasia.