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在阿根廷结直肠癌队列中使用BAT26作为单一标记物对微卫星不稳定性进行普遍测定。

Universal determination of microsatellite instability using BAT26 as a single marker in an Argentine colorectal cancer cohort.

作者信息

González María Laura, Causada-Calo Natalia, Santino Juan Pablo, Dominguez-Valentin Mev, Ferro Fabiana Alejandra, Sammartino Inés, Kalfayan Pablo Germán, Verzura Maria Alicia, Piñero Tamara Alejandra, Cajal Andrea Romina, Pavicic Walter, Vaccaro Carlos

机构信息

Programa de Cáncer Hereditario (ProCanHe), Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

Gastroenterology Department, Hospital Italiano de Buenos Aires, 4190 Juan D. Perón St. (C1199ABD), Buenos Aires, Argentina.

出版信息

Fam Cancer. 2018 Jul;17(3):395-402. doi: 10.1007/s10689-017-0052-4.

DOI:10.1007/s10689-017-0052-4
PMID:29128931
Abstract

Microsatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included. BAT26 determination was performed in all cases; if instability was found, immunohistochemistry (IHC) and BRAF mutation analyses were done, as appropriate. Differences were assessed by chi-squared or Fisher's exact test, or by T test or Mann-Whitney. Multiple logistic regression was used to identify factors independently associated with BAT26-unstable tumors. We included 155 patients; mean age was 65.6 (SD 14.4) and 56.1% were male. The frequency of BAT26-unstable tumors was 22% (95% CI 15.7-29.3). Factors independently associated with BAT26-unstable tumors were right colon localization (OR 3.4, 95% CI 1.3-8.7), histological MSI features (OR 5.1, 95% CI 1.9-13.6) and Amsterdam criteria (OR 23.2, 95% CI 1.9-286.7). IHC was altered in 85.3% BAT26-unstable tumors and 70.6% lacked MLH1 expression; 47.8% of these harbored BRAF V600E mutation. We provide evidence to link the frequency of BAT26 to an increased diagnostic yield (up to 1.4-folds) of suspected LS cases in comparison to the revised Bethesda guidelines alone. In regions with limited resources, clinical and histological features associated with BAT26-unstable status could be useful to direct MSI screening in sporadic CRCs and may help guide clinical care and future research.

摘要

微卫星不稳定性(MSI)是林奇综合征(LS)筛查的标志性工具,也是散发性结直肠癌(CRC)的预后标志物。在资源有限且CRC分子特征稀缺的地区,如南美洲,由于其目的,普遍MSI筛查的实施仍在争论中。我们试图估计结直肠腺癌中BAT26的频率,并确定相关的临床和组织学特征。纳入了CRC登记处的连续患者。对所有病例进行BAT26测定;如果发现不稳定性,则酌情进行免疫组织化学(IHC)和BRAF突变分析。通过卡方检验或费舍尔精确检验,或通过T检验或曼-惠特尼检验评估差异。使用多元逻辑回归来确定与BAT26不稳定肿瘤独立相关的因素。我们纳入了155例患者;平均年龄为65.6岁(标准差14.4),56.1%为男性。BAT26不稳定肿瘤的频率为22%(95%置信区间15.7-29.3)。与BAT26不稳定肿瘤独立相关的因素是右半结肠定位(比值比3.4,95%置信区间1.3-8.7)、组织学MSI特征(比值比5.1,95%置信区间1.9-13.6)和阿姆斯特丹标准(比值比23.2,95%置信区间1.9-286.7)。在85.3%的BAT26不稳定肿瘤中IHC发生改变,70.6%缺乏MLH1表达;其中47.8%携带BRAF V600E突变。我们提供证据表明,与仅修订的贝塞斯达指南相比,BAT26的频率与疑似LS病例的诊断率提高(高达1.4倍)相关。在资源有限的地区,与BAT26不稳定状态相关的临床和组织学特征可能有助于指导散发性CRC中的MSI筛查,并可能有助于指导临床护理和未来研究。

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