不同微卫星标记物组合在检测错配修复缺陷型结直肠肿瘤中的性能

Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors.

作者信息

Xicola Rosa M, Llor Xavier, Pons Elisenda, Castells Antoni, Alenda Cristina, Piñol Virgínia, Andreu Montserrat, Castellví-Bel Sergi, Payá Artemio, Jover Rodrigo, Bessa Xavier, Girós Anna, Duque José M, Nicolás-Pérez David, Garcia Ana M, Rigau Joaquin, Gassull Miquel A

机构信息

Department of Gastroenterology, Germans Trias i Pujol Hospital, Carretera del Canyet s/n, 08916 Badalona, Barcelona, Spain.

出版信息

J Natl Cancer Inst. 2007 Feb 7;99(3):244-52. doi: 10.1093/jnci/djk033.

DOI:10.1093/jnci/djk033

PMID:17284719

Abstract

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 [NCI] and a pentaplex of mononucleotide 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 NCI-recommended 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 mononucleotides 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 NCI panel were 76.5% (95% confidence interval [CI] = 61% to 92%) and 65.0% (95% CI = 49% to 81%), respectively; corresponding values for the mononucleotide pentaplex panel were 95.8% (95% CI = 89% to 103%) and 88.5% (95% CI = 79% to 98%), respectively. A panel consisting of the mononucleotide repeat markers BAT26 and NR24 alone had the same predictive value as the pentaplex panel of mononucleotide repeats.

CONCLUSIONS

The pentaplex panel of mononucleotide repeats performs better than the NCI 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.

摘要

背景

由DNA错配修复系统功能缺陷引起的结直肠肿瘤通常表现为微卫星不稳定。我们的目标是比较两组标志物（一组先前由美国国立癌症研究所[NCI]推荐，另一组为单核苷酸重复序列五重检测法）的性能，并设计出最简单的诊断策略，以识别具有错配修复缺陷特征的结直肠癌患者。

方法

我们招募了1058例新诊断为结直肠癌的患者。分别使用NCI推荐的微卫星标志物组和单核苷酸重复序列五重检测法作为聚合酶链反应（PCR）的模板，对新鲜冷冻和石蜡包埋肿瘤的DNA进行微卫星不稳定检测。在交叉分析中，也使用单核苷酸五重检测法评估新鲜冷冻肿瘤中的微卫星不稳定。通过免疫组织化学法测定肿瘤中错配修复蛋白（MLH1、MSH2、MSH6和PMS2）的表达。计算标志物组识别错配修复蛋白表达缺陷肿瘤的敏感性和特异性。所有统计检验均为双侧检验。

结果

NCI组的敏感性和阳性预测值分别为76.5%（95%置信区间[CI]=61%至92%）和65.0%（95%CI=49%至81%）；单核苷酸五重检测法的相应值分别为95.8%（95%CI=89%至103%）和88.5%（95%CI=79%至98%）。仅由单核苷酸重复标志物BAT26和NR24组成的一组与单核苷酸重复序列五重检测法具有相同的预测价值。