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

Abstract

Aims 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. Methods and results We identified 78 patients under surveillance for BO who had biopsies evaluated for abnormal p53 expression in conjunction with routine histology and 892 patients 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 5 years, 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. Conclusion 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.

The risk of neoplasia in patients with Barrett's esophagus indefinite for dysplasia: a multicenter cohort study

“…Furthermore, p53 protein expression assessment may help improve the agreement and reproducibility of the dysplasia diagnosis among pathologists. [31][32][33] However, we could not perform p53 immunohistochemistry on all of our cases because many were historical. The design of this study relied on standard hematoxylin and eosin staining in combination with other clinical and endoscopic data.…”

Combined histopathological risk score using TP53 protein expression, CD8+ T cell density and intratumoral budding is an independent predictor of neoadjuvant therapy response in rectal adenocarcinoma

“…However, this may be an oversimplification, as the TP53 null type pattern is not included. 32 In our study, we performed a pattern recognition method for assessing TP53 expression that has been described by Davison et al 33 as the optimal surrogate marker for TP53 mutations. The mutational pattern was interpreted when either complete loss of nuclear protein expression or strong homogenous overexpression was encountered.…”

Is Malignant Potential of Barrett’s Esophagus Predictable by Endoscopy Findings?

“…A progressive accumulation of LOH in esophageal lesions during the process of malignant transformation has been shown, with endoscopic brush cytology demonstrated to be effective for detection of LOH [ 83 ]. Another showed aberrant expression of p53 protein as a representative biomarker for prediction of neoplastic progression in BE [ 84 , 85 , 86 , 87 , 88 ]. Moreover, the TP53 mutation was found in 46% of patients with EAC progression [ 25 ], and reported to be associated with EAC progression with an OR of 3.18 (95% CI 1.68–6.03) [ 24 ] and an HR of 6.5 (95% CI 2.5–17.1) [ 89 ].…”