Genomic Biomarkers to Improve Ulcerative Colitis Neoplasia Surveillance
Genomic Biomarkers to Improve Ulcerative Colitis Neoplasia Surveillance
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DOI：
10.2353/ajpath.2008.080250
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发表时间：
2008-12-01
影响因子：
6
通讯作者：
Brentnall, Teresa A.
中科院分区：
文献类型：
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作者：
Bronner, Mary P.;O'Sullivan, Jacintha N.;Brentnall, Teresa A.
没有足够的手段来确定少数溃疡性结肠炎(UC)患者注定要经历肿瘤进展。认识到这一子集将通过将可用的管理选项集中在高风险患者上来推进UC癌症监测。三种不同的非增生性UC活检的基因组改变分析显示了区分肿瘤患者(UC进展者)和非UC非进展者(UC非进展者)的前景，包括端粒长度、后期桥和染色体荧光原位杂交的分析。扩大患者数量和在同一活检组织中同时进行化验进一步验证了它们的有效性。小组方法也改善了测试结果。共有14名UC进展者与15名非进展者和6名正常对照组分开。事实证明，染色体熵(即改变多样性的程度)是最有用的测试。通过受试者操作特征分析，28例患者的平均染色体熵对区分进展者和非进展者的敏感度为100%，特异度为92%，最佳阈值选择。此外，仅使用远离肿瘤的非发育不良和以直肠为主的活检(82.8%)可以实现分离，这表明对于大多数非进展型UC患者，完全结肠镜检查可以避免广泛的活检。这些数据进一步加强了基因组生物标记物可以区分UC进展者和非进展者的概念，并改善了UC的癌症监测。(Am J Pathol2008173：18531860年；DOI：10.2353/ajpath.2008.080250)
No adequate means exist to identify the minority of ulcerative colitis (UC) patients destined to undergo neoplastic progression. Recognition of this subset would advance UC cancer surveillance by focusing the available management options onto the highest risk patients. Three different assays of genomic alterations in nondysplastic UC biopsies show promise for distinguishing patients with neoplasia (UC progressors) from those without (UC nonprogressors), including assays of telomere length, anaphase bridges, and chromosomal fluorescence in situ hybridization. Expanding the number of patients and testing of assays simultaneously in the same biopsy further validated their utility. A panel approach also improved testing outcome. A total of 14 UC progressors was readily separable from 15 UC nonprogressors and 6 normal controls. Chromosomal entropy (ie, the extent of alteration diversity) proved to be the most useful test. By receiver-operating characteristic analysis, mean chromosomal entropy in 28 patients over all four chromosomes yielded 100% sensitivity and 92% specificity for distinguishing progressors from nonprogressors with optimum choice of threshold. Moreover, separation was achieved using only nondysplastic and predominantly rectal (82.8%) biopsies that were remote from neoplasia, suggesting that full colonoscopy with extensive biopsies might be avoided for the majority of UC patients, the nonprogressors. These data further strengthen the concept that genomic biomarkers can distinguish UC progressors from nonprogressors and improve cancer surveillance in UC. (Am J Pathol 2008, 173:1853-1860; DOI: 10.2353/ajpath.2008.080250)