Objective Whether 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. Design We 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). Results We found that 58 of 77 short-segment ( < 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<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. Conclusion SS-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. Data are available upon reasonable request. The sequencing data included in this study have been submitted to European Genome-phenome Archive (EGA; ) with accession numbers EGAD00001011188, EGAD00001011187 and EGAD00001011255.

中文翻译：

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了解食管胃化生的恶性潜力及其与巴雷特食管监测的相关性：个体水平数据分析

目的 食管胃上皮化生（GM）是否应被视为巴雷特食管（BO）尚存争议。考虑到取样可能会漏掉肠化生 (IM)，英国指南将 GM 列为 BO 的一种类型。在这里，我们调查了转基因的误诊风险和恶性潜力是否值得在英国监测中占有一席之地。设计 我们进行了彻底的病理学和内窥镜检查，以跟踪英国 244 名患者队列的临床结果，涵盖 1854 人年的随访。我们通过对 160 个 GM 和 IM 样本进行比较基因组分析来补充这一点，重点关注 BO 和食管腺癌 (OAC) 的早期分子标志。结果 我们发现，在中位 4.4 年的随访中，77 例短节段 ( < 3 cm) GM (SS-GM) 病例中有 58 例 (75%) 继续被观察为仅 GM。我们观察到，仅 GM 病例和 GM+IM 病例（在某些情况下报告 GM，在其他情况下报告 IM 的病例）的疾病进展显着低于仅 IM 病例（Kaplan-Meier，p=0.03）。基因组分析显示，GM 中的突变负担显着低于 IM（p<0.01）。此外，GM 不具有 OAC 的突变特征，不存在相关特征和驱动基因突变。最后，我们确定，与 OAC 相邻的 GM 在进化上与癌症相距甚远。结论 SS-GM与SS-IM是不同的实体，GM的恶性潜力低于IM。 SS-GM 是否值得纳入 BO 监视尚存疑问。数据可根据合理要求提供。本研究中包含的测序数据已提交给欧洲基因组-现象档案馆（EGA；），登录号为 EGAD00001011188、EGAD00001011187 和 EGAD00001011255。