采用免疫组织化学和基于微卫星不稳定性的检测策略检测子宫内膜癌患者的林奇综合征：检测准确性的系统评价。

Testing for lynch syndrome in people with endometrial cancer using immunohistochemistry and microsatellite instability-based testing strategies - A systematic review of test accuracy.

机构信息

Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.

Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom; Institute of Precision Diagnostics and Translational Medicine, University Hospital Coventry and Warwickshire (UHCW) NHS Trust, Coventry CV2 2DX, UK.

出版信息

Gynecol Oncol. 2021 Jan;160(1):148-160. doi: 10.1016/j.ygyno.2020.10.003. Epub 2020 Oct 24.

DOI:10.1016/j.ygyno.2020.10.003

PMID:33190932

Abstract

BACKGROUND

Lynch syndrome is an inherited genetic condition that is associated with an increased risk of cancer, including endometrial and colorectal cancer. We assessed the test accuracy of immunohistochemistry and microsatellite instability-based testing (with or without MLH1 promoter methylation testing) for Lynch syndrome in women with endometrial cancer.

METHODS

We conducted a systematic review of literature published up to August 2019. We searched bibliographic databases, contacted experts and checked reference lists of relevant studies. Two reviewers conducted each stage of the review.

RESULTS

Thirteen studies were identified that included approximately 3500 participants. None of the studies was at low risk of bias in all domains. Data could not be pooled due to the small number of heterogeneous studies. Sensitivity ranged from 60.7-100% for immunohistochemistry, 41.7-100% for microsatellite instability-based testing, and 90.5-100% for studies combining immunohistochemistry, microsatellite instability-based testing, and MLH1 promoter methylation testing. Specificity ranged from 60.9-83.3% (excluding 1 study with highly selective inclusion criteria) for immunohistochemistry, 69.2-89.9% for microsatellite instability-based testing, and 72.4-92.3% (excluding 1 study with highly selective inclusion criteria) for testing strategies that included immunohistochemistry, microsatellite instability-based testing, and MLH1 promoter methylation. We found no statistically significant differences in test accuracy estimates (sensitivity, specificity) in head-to-head studies of immunohistochemistry versus microsatellite instability-based testing. Reported test failures were rare.

CONCLUSIONS

Sensitivity of the index tests were generally high, though most studies had much lower specificity. We found no evidence that test accuracy differed between IHC and MSI based strategies. The evidence base is currently small and at high risk of bias.

摘要

背景

林奇综合征是一种遗传性疾病，与癌症风险增加有关，包括子宫内膜癌和结直肠癌。我们评估了免疫组织化学和基于微卫星不稳定性的检测（包括或不包括 MLH1 启动子甲基化检测）在子宫内膜癌患者中用于林奇综合征的检测准确性。

方法

我们对截至 2019 年 8 月发表的文献进行了系统评价。我们搜索了文献数据库，联系了专家，并检查了相关研究的参考文献列表。两名审查员进行了审查的每个阶段。

结果

确定了 13 项研究，其中包括约 3500 名参与者。没有一项研究在所有领域都存在低偏倚风险。由于研究数量较少且存在异质性，因此无法进行数据合并。免疫组织化学的敏感性范围为 60.7-100%，基于微卫星不稳定性的检测的敏感性范围为 41.7-100%，结合免疫组织化学、基于微卫星不稳定性的检测和 MLH1 启动子甲基化检测的研究的敏感性范围为 90.5-100%。特异性范围为 60.9-83.3%（排除 1 项具有高度选择性纳入标准的研究），基于微卫星不稳定性的检测的特异性范围为 69.2-89.9%，包括免疫组织化学、基于微卫星不稳定性的检测和 MLH1 启动子甲基化检测的检测策略的特异性范围为 72.4-92.3%（排除 1 项具有高度选择性纳入标准的研究）。我们在免疫组织化学与基于微卫星不稳定性的检测的头对头研究中没有发现检测准确性估计值（敏感性、特异性）的统计学差异。报告的检测失败很少见。