Sikkema Marjolein, Kerkhof Marjon, Steyerberg Ewout W, Kusters Johannes G, van Strien Paulina M H, Looman Caspar W N, van Dekken Herman, Siersema Peter D, Kuipers Ernst J
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Am J Gastroenterol. 2009 Nov;104(11):2673-80. doi: 10.1038/ajg.2009.437. Epub 2009 Jul 28.
Surveillance of patients with Barrett's esophagus (BE) aims at early detection and treatment of neoplastic changes, particularly esophageal adenocarcinoma (EAC). The histological evaluation of biopsy samples has its limitations, and biomarkers may improve early identification of BE patients at risk for progression to EAC. The aim of this study was to determine the predictive value of p53, Ki67, and aneuploidy as markers of neoplastic progression in BE.
A total of 27 BE patients with histologically proven progression to high-grade dysplasia (HGD) or EAC (cases) and 27 BE patients without progression (controls) were selected and matched for age, gender, and duration of follow-up. Dysplasia grade was determined in 212 biopsy samples obtained during surveillance endoscopies from cases and in 231 biopsy samples collected from controls. DNA ploidy status was determined by flow cytometry, whereas Ki67 and p53 expression was determined by immunohistochemistry. Hazard ratios (HRs) were calculated by Cox regression adjusted for potentially confounding variables.
A univariate analysis showed that low-grade dysplasia (LGD) increased the risk of developing HGD/EAC compared with no dysplasia (HR 3.6; 95% confidence interval (CI): 1.6 - 8.1). Aneuploidy (HR 3.5; 95% CI: 1.3-9.4), strong Ki67 overexpression (HR 5.2; 95% CI: 1.5-17.6), and moderate p53 overexpression (HR 6.5; 95% CI: 2.5-17.1) were also associated with an increased risk of developing HGD/EAC, independent of the histological result. A multivariable analysis showed that in the presence of LGD, p53 overexpression, and to a lesser extent, Ki67 overexpression remained important risk factors for neoplastic progression, whereas aneuploidy was no longer predictive.
p53 overexpression and, to a lesser extent, Ki67 overexpression could predict neoplastic progression in BE irrespective of the histological result. These markers may be useful for identifying patients at an increased risk of developing EAC, either alone or used as a panel.
对巴雷特食管（BE）患者进行监测旨在早期发现并治疗肿瘤性改变，尤其是食管腺癌（EAC）。活检样本的组织学评估存在局限性，生物标志物可能有助于早期识别有进展为EAC风险的BE患者。本研究的目的是确定p53、Ki67和非整倍体作为BE肿瘤进展标志物的预测价值。
共选取27例经组织学证实进展为高级别异型增生（HGD）或EAC的BE患者（病例组）和27例无进展的BE患者（对照组），并根据年龄、性别和随访时间进行匹配。在病例组监测内镜检查期间获取的212份活检样本以及对照组收集的231份活检样本中确定异型增生分级。通过流式细胞术确定DNA倍体状态，而通过免疫组织化学确定Ki67和p53表达。通过对潜在混杂变量进行校正的Cox回归计算风险比（HRs）。
单因素分析显示，与无异型增生相比，低级别异型增生（LGD）增加了发生HGD/EAC的风险（HR 3.6；95%置信区间（CI）：1.6 - 8.1）。非整倍体（HR 3.5；95% CI：1.3 - 9.4）、Ki67强过表达（HR 5.2；95% CI：1.5 - 17.6）和p53中度过表达（HR 6.5；95% CI：2.5 - 17.1）也与发生HGD/EAC的风险增加相关，且与组织学结果无关。多变量分析显示，在存在LGD的情况下，p53过表达以及在较小程度上Ki67过表达仍然是肿瘤进展的重要危险因素，而非整倍体不再具有预测性。
p53过表达以及在较小程度上Ki67过表达可预测BE的肿瘤进展，而与组织学结果无关。这些标志物单独或作为一个组合，可能有助于识别发生EAC风险增加的患者。
Zotero 插件