Analysis of Ki-67, p53 and Bcl-2 expression in the dysplasia-carcinoma sequence of Barrett's esophagus

The grading of dysplasia in Barrett's esophagus has prognostic importance, however observer variation limits the reliability of simple histological an alysis alone. We investigated Ki-67, p53 and Bcl-2 expression in Barrett's esophagus, in the sequence from Barrett's low-grade dysplasia to high-grade dysplasia and infiltrating adenocarcinoma. Forty-four esophagectomy specim ens were utilized: 39 specimens with esophageal dysplasia and adenocarcinom a and 5 specimens with esophageal dysplasia only. This gave 83 sections (2 sections for specimens with dysplasia and carcinoma) examined from 44 patie nts. The sections were examined for Ki-67, p53 and Bcl-2 reactivity by immu nohistochemistry. Low-grade dysplasia was present in 14 sections, high-grad e dysplasia in 30 sections and carcinoma in 39 sections. Ki-67 expression o ccurred in 2 out of 14 (14%) sections with low-grade dysplasia, in 22 out o f 30 (73%) sections with high-grade dysplasia and in 34 out of 39 (87%) sec tions with carcinoma (p<0.001), p53 protein expression was found in 1 of 14 (7%) sections with low-grade dysplasia, in 18 of 30 (60%) sections with hi gh-grade dysplasia and in 33 of 39 (85%) sections with carcinoma (p<0.001). Expression of Bcl-2 was found in 11 of 14 (84%) sections with low-grade dy splasia but immunoreactivity was not seen in any section with high-grade dy splasia or Barrett's carcinoma. Our results indicate that overexpression of Ki-67, Bcl-2 protein and p53 mutations can be identified as early events d uring neoplastic progression in Barrett's esophagus. These data support the hypothesis that, in the progression of Barrett's metaplasia to adenocarcin oma, the balance of proliferation/apoptosis plays an important role.