Defining an abnormal p53 immunohistochemical stain in Barrett's oesophagus-related dysplasia: a single-positive crypt is a sensitive and specific marker of dysplasia.

ABSTRACT

AIMS: p53 is an independent risk stratification marker in Barrett's oesophagus (BE), but no universally accepted definition exists for abnormal p53 staining. Herein, we assess p53 stains in two cohorts to (1) define abnormal p53 staining in BE-related dysplasia (BERD) and (2) assess the specificity and sensitivity of this cut-point for the diagnosis of dysplasia. METHODS: Cohort 1 (n = 313) included (1) dysplastic BE biopsies, (2) prior non-dysplastic BE (NDBE) biopsies from the same patients and (3) NDBE biopsies from patients who never progressed to dysplasia. Cohort 2 (n = 191) consisted of BE biopsies in which p53 staining aided in diagnosing dysplasia. Automated p53 staining quantification was performed on cohort 1. A semiquantitative p53 analysis, performed on both cohorts, included (1) number of strongly positive glands, (2) strong glandular surface staining, (3) percentage of strongly positive glands and (4) null phenotype. RESULTS: NDBE biopsies from cohort 1 patients who progressed to dysplasia were more likely to show p53 positivity than non-progressors (16.9 versus 0.6%) (P = 0.0001). The optimal quantitative cut-point for distinguishing dysplastic from never-dysplasia biopsies was 10 strongly positive cells. By semiquantitative analysis, a single strongly p53-positive gland distinguished dysplastic from never-dysplasia BE (sensitivity 98.6%, specificity 99.4%). The semiquantitative and quantitative analyses correlated (P = 0.0001). In cohort 2, the sensitivity and specificity for BERD of ≥ 1 strongly positive p53 gland were 86.0 and 88.6%. CONCLUSIONS: A single strongly positive p53 gland is sensitive and specific for BERD. Automated p53 analysis may reduce subjectivity associated with the diagnosis of BERD.