Use of p53 immunohistochemistry in conjunction with routine histology improves risk stratification of patients with Barrett's oesophagus during routine clinical care.

Abstract

Abnormal p53 protein expression detected by immunohistochemistry (IHC) in Barrett's oesophagus (BO) is reported to be a prognostic biomarker for progression to high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC). We evaluated our use of p53 IHC for patients with BO under surveillance from 2010 to 2016 in a single academic institution. We identified 78patients under surveillance for BO who had biopsies evaluated for abnormal p53 expression in conjunction with routine histology and 892patients who had histological evaluation alone. All available p53 IHC slides were rescored as wild-type or abnormal. We evaluated the risk of subsequent diagnosis with HGD and OAC. p53-tested patients were significantly more likely to be diagnosed with indefinite dysplasia (IND) or low-grade dysplasia (LGD), compared to patients who were not tested (79.5 versus 10.8%, P=7.4×10-40 ). Almost half (46.9%) of patients with abnormal p53 expression were diagnosed with HGD or OAC within 5years, compared to 5.9% with wild-type p53, and 7.6% of patients not tested (P=2.6×10-18 ). However, this difference was heavily influenced by other risk factors, including dysplasia grade, in multivariate analyses. In the subgroup of patients diagnosed with IND (n=109), abnormal p53 expression was associated with a fourfold increase (1.2-13.3, P=0.023) in risk of HGD/OAC relative to untested patients diagnosed with IND, independent of other risk factors. In patients under surveillance for BO in a single academic institution, we found evidence that selective use of p53 IHC in conjunction with routine histology modestly improved risk stratification by identifying patients with IND at higher risk of a subsequent diagnosis of HGD or OAC.