Understanding the malignant potential of gastric metaplasia of the oesophagus and its relevance to Barrett’s oesophagus surveillance: individual-level data analysis

Abstract

Peer reviewed: TrueAcknowledgements: We sincerely thank Judith Honing for the help and guidance on assessing clinical outcomes, and Massimiliano di Pietro for helpful discussions. We thank Elwira Merry for organising the collection of tissue blocks, and Alex Northrop and Conor Flint for assisting with tissue extraction. We thank Lizhe Zhuang for histopathology images. We thank the Human Research Tissue Bank, which is supported by the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, from Addenbrooke’s Hospital. Figure 1 was created with BioRender.com.ObjectiveWhether gastric metaplasia (GM) of the oesophagus should be considered as Barrett’s oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance.DesignWe performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC).ResultsWe found that 58 of 77 short-segment (&lt;3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was significantly lower than in the IM-only cases (Kaplan-Meier, p=0.03). Genomic analysis revealed that the mutation burden in GM is significantly lower than in IM (p&lt;0.01). Moreover, GM does not bear the mutational hallmarks of OAC, with an absence of associated signatures and driver gene mutations. Finally, we established that GM found adjacent to OAC is evolutionarily distant from cancer.ConclusionSS-GM is a distinct entity from SS-IM and the malignant potential of GM is lower than IM. It is questionable whether SS-GM warrants inclusion in BO surveillance.</jats:sec