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生物标志物的异常表达与巴雷特食管发育异常肿瘤性变化的风险预测

The Aberrant Expression of Biomarkers and Risk Prediction for Neoplastic Changes in Barrett's Esophagus-Dysplasia.

作者信息

Choi Young, Bedford Andrew, Pollack Simcha

机构信息

Department of Pathology, Yale School of Medicine, 434 Pine Grove Lane, Hartsdale, NY 10530, USA.

Department of Internal Medicine, Yale School of Medicine, Bridgeport Hospital, 267 Grant St., Bridgeport, CT 06610, USA.

出版信息

Cancers (Basel). 2024 Jun 28;16(13):2386. doi: 10.3390/cancers16132386.

Abstract

: 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. : 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. : 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. : 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

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患者的管理。然而,BE可能被漏诊,且基于常规组织学对异型增生进行准确分级存在较大的观察者内和观察者间差异。因此,明确的生物标志物检测仍然不可或缺。我们研究的目的是确定常规适用且相对特异的生物标志物,用于准确诊断BE,并确定预测BE异型增生进展风险的生物标志物。

回顾性地,我们对活检组织进行免疫组织化学检测,以检测黏蛋白2(MUC2)、三叶因子3(TFF3)、p53、p16、细胞周期蛋白D1、Ki-67、β-连环蛋白和微小染色体维持蛋白(MCM2)。前瞻性地,为了识别染色体改变,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。

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,与低级别异型增生(LGD)、高级别异型增生(HGD)和EAC组织学显著相关,肿瘤性改变风险相对较高。此外,BE不确定异型增生(IND)进展队列中p53和p16的异常表达预测了进展风险。

评估这些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异型增生分级的准确性,从而减少观察者间差异,尤其是LGD和风险预测方面的差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21f3/11240336/0b442c31491f/cancers-16-02386-g001.jpg

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