The future is now: advancing p53 immunohistochemistry in Barrett's oesophagus and its implication for the everyday pathologist.

Barrett's oesophagus (BE) is a precancerous condition where the normal squamous epithelium of the distal oesophagus is replaced by specialised intestinal-type columnar epithelium. Patients with BE have an increased risk of developing oesophageal adenocarcinoma (EAC). p53 is a tumour suppressor protein frequently mutated in BE, and its overexpression is detectable by immunohistochemistry (IHC) and correlates with TP53 mutations. This review summarises recent literature on p53 IHC as a diagnostic aid for dysplasia and a predictive biomarker of neoplastic progression risk in BE. While there is a vast amount of literature on this topic, there are no established criteria for what constitutes an abnormal p53 immunohistochemical result in the setting of BE. Multiple studies show that p53 IHC improves interobserver agreement and diagnostic confidence for low-grade dysplasia, high-grade dysplasia and EAC compared to histology alone. Establishing easy-to-use, reproducible and practical diagnostic criteria that can be applied to routine daily practice is urgently needed. p53 IHC overexpression in non-dysplastic BE indicates an increased neoplastic progression risk. Emerging technologies such as next-generation sequencing may offer higher sensitivity for detecting neoplastic clones. While the haematoxylin and eosin stain remains the most powerful tool, p53 IHC is a valuable adjunct for determining and diagnosing dysplasia. Although p53 is helpful in predicting the risk of dysplasia in non-dysplastic Barrett's oesophagus, its sensitivity is low, limiting its routine use in this context.