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Abstract：
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.
摘要：
背景：Barrett食管（BE）是一种与食管腺癌（EAC）风险增加相关的癌前病变。BE的准确诊断和发育不良的分级有助于优化BE患者的管理。然而,可能会错过BE，并且基于常规组织学对发育不良的准确分级具有相当大的观察者内部和观察者之间的差异。因此，明确定义的生物标志物测试仍然是不可或缺的。我们研究的目的是确定常规适用和相对特异性的生物标志物，以准确诊断BE。以及确定生物标志物来预测BE发育不良的进展风险。方法:回顾性,我们进行了免疫组织化学检测粘蛋白2（MUC2），三叶因子3(TFF3)，p53，p16，细胞周期蛋白D1，Ki-67，β-catenin，和活检中的微小染色体维持（MCM2）。Prospective,为了识别染色体改变，我们对内镜监测时收集的新鲜毛刷样本进行了荧光原位杂交检测.结果：我们发现MUC2和TFF3是诊断BE的特异性标志物。异常表达，包括p53，Ki-67，p16，β-catenin的丢失和强烈过表达，细胞周期蛋白D1和MCM2与低度发育不良（LGD）显着相关，高度发育不良（HGD），和EAC组织学，肿瘤改变的风险相对较高。此外，BE不确定发育不良(IND)进展队列中p53和p16的异常表达预测了进展的风险.结论：评估生物标志物将是准确的BE组织学诊断的合适辅助手段，并提高BE发育不良分级的准确性。从而减少观察者间的可变性，特别是LGD和风险预测。
