Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors
Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors
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DOI：
10.1093/jnci/djk033
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发表时间：
2007-02-07
影响因子：
10.3
通讯作者：
Gassull, Miquel A.
中科院分区：
文献类型：
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作者：
Xicola, Rosa M.;Llor, Xavier;Gassull, Miquel A.
背景由于DNA错配修复系统的失败而导致的结直肠肿瘤通常表现为微卫星不稳定性。我们的目标是比较两个小组的标志物（一个小组以前建议由美国国家癌症研究所[NCl]和monoparticle repeats的五重）的性能，并制定最简单的诊断策略，以确定患者的特征在于错配repair.Methods缺陷的结直肠癌患者招募了1058例新诊断为结直肠癌。新鲜冷冻和石蜡包埋的肿瘤DNA进行了测试的微卫星不稳定性，使用NC 1-recommencled面板的微卫星标记和五重面板的monoclantide重复，分别作为聚合酶链反应（PCR）的模板。新鲜冷冻肿瘤中的微卫星不稳定性也在交叉分析中使用monoclonal antibodies的pentaplex panel进行评估。免疫组化法检测错配修复蛋白（MLH 1、MSH 2、MSH 6和PMS 2）在肿瘤中的表达。计算标志物组鉴定错配修复蛋白表达缺陷的肿瘤的灵敏度和特异性。结果NCI组的敏感性和阳性预测值为76.5%（95%置信区间[CI] 61%至92%）和65.0%（95% CI = 49%-81%）;单颗粒五重组的相应值分别为95.8%（95%CI = 89%至103%）和88.5%（95%CI = 79%至98%）。一个面板组成的monoparticle重复标记BAT 26和NR 24单独具有相同的预测值的monoparticle repeats.ConCIusions的monoparticle重复的pentaplex面板比NC 1面板错配修复缺陷肿瘤的检测。同时评估BAT 26和NR 24的不稳定性与使用五元组诊断错配修复缺陷一样有效。
Background Colorectal tumors caused by failure of the DNA mismatch repair system commonly show microsatellite instability. Our goals were to compare the performance of two panels of markers (a panel previously recommended by the National Cancer Institute [NCl] and a pentaplex of mononucleoticle repeats) and to devise the simplest diagnostic strategy for identification of patients with colorectal cancer characterized by defects in mismatch repair.Methods We recruited 1058 patients who were newly diagnosed with colorectal cancer. DNA from fresh-frozen and paraffin-embedded tumors was tested for microsatellite instability, using the NCl-recommencled panel of microsatellite markers and the pentaplex panel of mononucleotide repeats, respectively, as templates for polymerase chain reactions (PCRs). Microsatellite instability in fresh-frozen tumors was also assessed using the pentaplex panel of mononucleoticles in a crossover analysis. The expression of mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) in the tumors was determined immunohistochemically. The sensitivity and specificity with which the marker panels identified tumors with deficiencies in the expression of mismatch repair proteins were calculated. All statistical tests were two-sided.Results The sensitivity and positive predictive value of the NCl panel were 76.5% (95% confidence interval [CI] 61% to 92%) and 65.0% (95% CI = 49% to 81%), respectively; corresponding values for the mononucleoticle pentaplex panel were 95.8% (95% CI = 89% to 103%) and 88.5% (95% CI = 79% to 98%), respectively. A panel consisting of the mononucleoticle repeat markers BAT26 and NR24 alone had the same predictive value as the pentaplex panel of mononucleoticle repeats.ConCIusions The pentaplex panel of mononucleoticle repeats performs better than the NCl panel for the detection of mismatch repair-deficient tumors. Simultaneous assessment of the instability of BAT26 and NR24 is as effective as use of the pentaplex panel for diagnosing mismatch repair deficiency.