Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK.
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Gut. 2024 Apr 5;73(5):729-740. doi: 10.1136/gutjnl-2023-330721.
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.
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).
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.
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.
食管胃黏膜上皮化生（GM）是否应被视为 Barrett 食管（BO）存在争议。由于担心由于采样而漏诊肠上皮化生（IM），英国指南将 GM 纳入 BO 类型。在此，我们研究了 GM 误诊风险和恶性潜能是否使其有资格进入英国监测范围。
我们对 244 例新的英国患者进行了彻底的病理和内镜检查，以随访其临床结局，共随访了 1854 人年。我们通过对 160 例 GM 和 IM 标本的比较基因组分析对此进行了补充，重点是 BO 和食管腺癌（OAC）的早期分子标志。
我们发现，77 例短节段（3cm）GM（SS-GM）中，有 58 例（75%）在中位 4.4 年的随访中继续观察为 GM 仅存在。我们观察到 GM 仅存在和 GM+IM 存在病例（有时报告 GM，有时报告 IM）的疾病进展明显低于 IM 仅存在病例（Kaplan-Meier，p=0.03）。基因组分析显示 GM 的突变负担明显低于 IM（p<0.01）。此外，GM 不具有 OAC 的突变特征，不存在相关的特征和驱动基因突变。最后，我们确定与 OAC 相邻的 GM 在进化上与癌症不同。
SS-GM 与 SS-IM 不同，GM 的恶性潜能低于 IM。SS-GM 是否应纳入 BO 监测范围值得怀疑。
