Background: A histological diagnosis of dysplasia is our current best predictor of progression in Barrett’s esophagus (BE), the precursor of esophageal adenocarcinoma (EAC). Despite periodic endoscopic surveillance and assessment of dysplastic changes, we fail to identify the majority of those who progress before the development of EAC, whereas the majority of patients undergo endoscopy without showing progression. Summary: Low-grade dysplasia (LGD), confirmed by expert pathologists, identifies BE patients at higher risk for progression, but the diagnosis of LGD is challenging. Recent research indicates that progression from BE to EAC is heterogeneous and can accelerate via genome doubling and genome catastrophes, resulting in different ways to progression. We identified 3 target areas, which may help to overcome the current lack of an accurate biomarker: (1) the implementation of somatic point mutations, chromosomal alterations, and epigenetic changes (genomics and epigenomics), (2) evaluate and develop biomarkers over space and time, (3) use new sampling methods such as noninvasive self-expandable sponges and endoscopic brushes. This review focus on the state of the art in risk stratifying BE and on recent advances which may overcome the limitations of current strategies. Key Messages: A panel of clinical factors, genomics, epigenomics, and/or proteomics will most likely lead to an assay that accurately risk stratifies BE patients into low- or high-risk for progression. This biomarker panel needs to be developed and validated in large cohorts containing a sufficient number of progressors, with testing samples over space (spatial distribution) and time (temporal distribution). For implementation in clinical practice, the technique should be affordable and applicable to formalin-fixed paraffin-embedded samples, which represent standard of care.
Visc Med

中文翻译：

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Barrett 食管生物标志物的开发和使用中今天的错误和明天的智慧

背景：异型增生的组织学诊断是我们目前预测巴雷特食管 (BE) 进展的最佳指标，巴雷特食管是食管腺癌 (EAC) 的前体。尽管定期进行内窥镜监测和评估发育不良变化，但我们未能确定大多数在 EAC 发展之前进展的患者，而大多数患者接受内窥镜检查而未显示进展。概括：经专家病理学家确认的低度异型增生 (LGD) 可识别出进展风险较高的 BE 患者，但 LGD 的诊断具有挑战性。最近的研究表明，从 BE 到 EAC 的进展是异质的，并且可以通过基因组加倍和基因组灾难加速，从而导致不同的进展方式。我们确定了 3 个目标领域，这可能有助于克服目前缺乏准确生物标志物的问题：(1) 体细胞点突变、染色体改变和表观遗传学变化（基因组学和表观基因组学）的实施，(2) 评估和开发空间生物标志物和时间，（3）使用新的取样方法，如无创自膨胀海绵和内窥镜刷。关键信息：一组临床因素、基因组学、表观基因组学和/或蛋白质组学很可能会导致一项分析，该分析可以准确地将 BE 患者风险分层为进展的低风险或高风险。该生物标志物组需要在包含足够数量进展者的大型队列中开发和验证，并在空间（空间分布）和时间（时间分布）上测试样本。为了在临床实践中实施，该技术应该是负担得起的，并且适用于代表护理标准的福尔马林固定石蜡包埋样品。
维斯克医学