Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer
Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer
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DOI：
10.1016/j.urolonc.2016.02.011
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发表时间：
2016-06-01
影响因子：
2.7
通讯作者：
DeGraff, David J.
中科院分区：
文献类型：
--
作者：
Warrick, Joshua I.;Raman, Jay D.;DeGraff, David J.
背景：评价ZEST同源基因增强子2(EZH2)在膀胱癌中的表达和肿瘤预后的研究一直存在差异。EZH2在非浸润性膀胱癌中的表达尚未得到很好的研究。因此，我们着手解决以往报道中的差异，并在一个大型膀胱切除术队列中研究EZH2在非侵袭性膀胱癌中的表达及其相关性。材料和方法：在组织微阵列材料(侵袭性和非侵袭性癌症)中评估EZH2的表达。确定EZH2的表达与肿瘤预后、肿瘤分期和疾病类型之间的关系。结果：EZH2在浸润性癌和扁平原位癌中的表达最常见，其次为浸润性癌、非浸润性乳头状尿路上皮癌和良性尿路上皮癌(P<；0.05均为直线模型)。受试者工作特性分析显示，与良性尿路上皮相比，CIS的曲线下面积为0.92，浸润性癌的曲线下面积为0.83。以~gt；4为界值时，对CIS和浸润性癌的敏感性分别为%和73%，特异性分别为82%和82%。EZH2的表达与肿瘤预后无关，包括无复发生存率和膀胱癌死亡。同一膀胱非浸润性癌和浸润性膀胱癌的EZH2表达状态(阳性或阴性)相关(P=0.05，Fisher准确)。结论：EZH2基因在非浸润性和浸润性膀胱癌中的表达存在个体相关性，提示EZH2可能是一种谱系标志。EZH2可提供诊断实用价值，特别是在扁平尿路上皮CIS与良性尿路上皮之间。本研究支持EZH2在膀胱癌中的表达不能预测肿瘤预后。(C)2016 Elsevier Inc.保留所有权利。
Background: Studies evaluating enhancer of zeste homolog 2 (EZH2) expression and oncologic outcomes in bladder cancer have been discrepant. EZH2 expression in noninvasive bladder cancer is not well studied. We thus set out to address the discrepancy in previous reports, and to study expression of EZH2 in noninvasive bladder cancer and its associations, in a large cystectomy cohort.Materials and methods: EZH2 expression was evaluated in tissue microarray material (invasive and noninvasive cancer). Associations between EZH2 expression and oncologic outcomes, tumor stage, and disease type were determined. Receiver operating characteristic analysis was performed for EZH2 expression in the diagnosis of invasive carcinoma and flat carcinoma in situ (CIS) compared to benign urothelium.Results: EZH2 expression was most common in CIS, followed by invasive carcinoma, noninvasive papillary urothelial carcinoma, and benign urothelium, in decreasing order (P < 0.05 all comparisons, linear model). The receiver operating characteristic analysis demonstrated an area under the curve of 0.92 for CIS and 0.83 for invasive carcinoma, both compared to benign urothelium. At a cutoff of >4, this corresponded to sensitivities of 89% and 73%, and specificities of 82% and 82%, for CIS and invasive carcinoma, respectively. The EZH2 expression was not associated with oncologic outcomes, including recurrence-free survival and death from bladder cancer. The EZH2 expression status (positive or negative) of noninvasive and invasive carcinomas taken from the same bladder correlated (P = 0.05, Fisher exact).Conclusion: That EZH2 status of noninvasive and invasive cancer correlated in individual patients suggests that EZH2 may be a marker of lineage. EZH2 may offer diagnostic utility, particularly in flat urothelial CIS vs. benign urothelium. The present study supports that EZH2 expression in bladder cancer is not predictive of oncologic outcome. (c) 2016 Elsevier Inc. All rights reserved.