Background: Barrett’s esophagus (BE) is a pre-neoplastic condition associated with an increased risk of esophageal adenocarcinoma (EAC). The accurate diagnosis of BE and grading of dysplasia can help to optimize the management of patients with BE. However, BE may be missed and the accurate grading of dysplasia based on a routine histology has a considerable intra- and interobserver variability. Thus, well-defined biomarker testing remains indispensable. The aim of our study was to identify routinely applicable and relatively specific biomarkers for an accurate diagnosis of BE, as well as determining biomarkers to predict the risk of progression in BE–dysplasia.Methods: Retrospectively, we performed immunohistochemistry to test mucin 2(MUC2), trefoil factor 3 (TFF3), p53, p16, cyclin D1, Ki-67, beta-catenin, and minichromosome maintenance (MCM2) in biopsies. Prospectively, to identify chromosomal alterations, we conducted fluorescent in situ hybridization testing on fresh brush samples collected at the time of endoscopy surveillance.Results: We discovered that MUC2 and TFF3 are specific markers for the diagnosis of BE. Aberrant expression, including the loss and strong overexpression of p53, Ki-67, p16, beta-catenin, cyclin D1, and MCM2, was significantly associated with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC histology, with a relatively high risk of neoplastic changes. Furthermore, the aberrant expressions of p53 and p16 in BE-indefinite dysplasia (IND) progressor cohorts predicted the risk of progression.Conclusions: Assessing the biomarkers would be a suitable adjunct to accurate BE histology diagnoses and improve the accuracy of BE–dysplasia grading, thus reducing interobserver variability, particularly of LGD and risk prediction.
背景：巴雷特食管（BE）是一种癌前病变，与食管腺癌（EAC）风险增加相关。准确诊断BE及异型增生分级有助于优化BE患者管理。然而，BE可能被漏诊，且基于常规组织学的异型增生准确分级存在显著的观察者内及观察者间差异。因此，明确的生物标志物检测仍不可或缺。本研究旨在识别适用于常规诊断且相对特异的BE诊断生物标志物，并确定可预测BE-异型增生进展风险的生物标志物。 方法：回顾性研究中，我们采用免疫组织化学方法检测活检组织中黏蛋白2（MUC2）、三叶因子3（TFF3）、p53、p16、细胞周期蛋白D1、Ki-67、β-连环蛋白及微小染色体维持蛋白2（MCM2）的表达。前瞻性研究中，为识别染色体改变，我们对内镜监测时采集的新鲜刷检样本进行荧光原位杂交检测。 结果：我们发现MUC2和TFF3是诊断BE的特异性标志物。p53、Ki-67、p16、β-连环蛋白、细胞周期蛋白D1和MCM2的异常表达（包括缺失和强过表达）与低度异型增生（LGD）、高度异型增生（HGD）及EAC组织学显著相关，且提示较高的瘤变风险。此外，在BE-不确定异型增生（IND）进展队列中，p53和p16的异常表达可预测进展风险。 结论：生物标志物评估可作为BE组织学准确诊断的适宜辅助手段，提高BE-异型增生分级的准确性，从而减少观察者间差异，尤其对LGD诊断及风险预测具有重要价值。
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