Journal
HISTOPATHOLOGY
Volume 71, Issue 1, Pages 27-33Publisher
WILEY
DOI: 10.1111/his.13193
Keywords
Barrett's oesophagus; dysplasia; immunohistochemistry; oesophageal cancer
Categories
Funding
- National Institutes of Health [R01 CA81570]
- Eisai Inc.
- Ortho-McNeil Janssen Scientific Affairs, LLC
- Ertan Educational/Research Foundation
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Aims: The purpose of this study was to determine prospectively whether p53 protein accumulation in biopsies of Barrett's metaplasia (BM) is a predictor of malignant progression, without relying on dysplasia grading. Methods and results: Sections of formalin-fixed paraffin-embedded tissue from the initial biopsies of 275 patients with BM, who had no high-grade dysplasia (HGD) or oesophageal adenocarcinoma (EAC), were stained for p53 by immunohistochemistry. The mean follow-up was 41 months. p53-positive biopsies were divided into four groups: scattered positive cells, multifocal scattered positive cells, aggregates of positive cells, and multifocal aggregates of positive cells. Kaplan-Meier analysis with the log-rank test was used to determine the rate of progression to HGD/EAC. Of the 275 patients, 227 had initial biopsies that were completely negative for p53, and, of these, one (0.4%) progressed to HGD/EAC; none of 24 (0%) patients with scattered positive cells and none of four (0%) of patients with multifocal scattered positive cells progressed. In contrast, five of 16 (31.25%) patients with aggregates of positive cells and three of four (75%) of those with multifocal aggregates of positive cells progressed to HGD/EAC. Kaplan-Meier analysis with log-rank statistics showed the difference in progression rate between the five groups to be highly significant (P < 0.0001). Conclusions: We conclude that p53 protein accumulation, detected by immunohistochemistry in aggregates of cells, is a significant predictor of malignant progression in patients with BM.
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