Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, New York.
Department of Information Technologies and Services, Weill Cornell Medical College, New York, New York.
Cancer. 2019 Sep 15;125(18):3172-3183. doi: 10.1002/cncr.32203. Epub 2019 May 31.
Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer to identify those with underlying Lynch syndrome. However, the effectiveness of these screening methods in identifying individuals with Lynch syndrome across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), mutL homolog 1 (MLH1) methylation, and microsatellite instability (MSI) analysis among patients with endometrial cancer.
A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for 1990-2018 was performed. A DerSimonian-Laird random effects model meta-analysis was used to estimate the weighted prevalence of Lynch syndrome diagnoses.
The comprehensive search produced 4400 publications. Twenty-nine peer-reviewed studies met the inclusion criteria. Patients with endometrial cancer (n = 6649) were identified, and 206 (3%) were confirmed to have Lynch syndrome through germline genetic testing after positive universal tumor molecular screening. Among 5917 patients who underwent tumor IHC, 28% had abnormal staining. Among 3140 patients who underwent MSI analysis, 31% had MSI. Among patients with endometrial cancer, the weighted prevalence of Lynch syndrome germline mutations was 15% (95% confidence interval [CI], 11%-18%) with deficient IHC staining and 19% (95% CI, 13%-26%) with a positive MSI analysis. Among 1159 patients who exhibited a loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation-negative among those who underwent methylation testing, and 32 demonstrated a germline MLH1 mutation (2.8% of all absent MLH1 staining cases and 22.4% of all MLH1 methylation-negative cases). Forty-three percent of patients with endometrial cancer who were diagnosed with Lynch syndrome via tumor typing would have been missed by family history-based screening alone.
Despite the widespread implementation of universal tumor testing in endometrial cancer, data regarding testing results remain limited. This study provides predictive values that will help practitioners to evaluate abnormal results in the context of Lynch syndrome and aid them in patient counseling.
建议所有被诊断患有子宫内膜癌的女性都进行通用肿瘤检测，以识别潜在的林奇综合征患者。然而，这些筛查方法在人群中识别林奇综合征个体的有效性尚未得到很好的研究。本研究旨在评估子宫内膜癌患者中错配修复缺陷（MMR）免疫组化（IHC）、MutL 同系物 1（MLH1）甲基化和微卫星不稳定性（MSI）分析的结果。
对 1990 年至 2018 年的在线数据库（PubMed、EMBASE、MEDLINE 和 Cochrane Library）进行了全面系统的搜索。采用 DerSimonian-Laird 随机效应模型荟萃分析来估计林奇综合征诊断的加权患病率。
全面搜索产生了 4400 篇出版物。29 项经过同行评审的研究符合纳入标准。共确定了 6649 例患有子宫内膜癌的患者，在对阳性的通用肿瘤分子筛查后，通过种系基因检测证实 206 例（3%）患有林奇综合征。在 5917 例行肿瘤 IHC 的患者中，有 28%的患者染色异常。在 3140 例行 MSI 分析的患者中，有 31%的患者 MSI 阳性。在患有子宫内膜癌的患者中，林奇综合征种系突变的加权患病率为 15%（95%置信区间[CI]，11%-18%），IHC 染色缺失和 MSI 阳性分析的阳性率分别为 19%（95%CI，13%-26%）。在 1159 例出现 MLH1 染色缺失的患者中，143 例（13.7%）经甲基化检测为 MLH1 甲基化阴性，32 例显示种系 MLH1 突变（所有缺失 MLH1 染色病例的 2.8%和所有 MLH1 甲基化阴性病例的 22.4%）。通过肿瘤分型诊断为林奇综合征的子宫内膜癌患者中有 43%仅通过家族史筛查会被遗漏。
尽管在子宫内膜癌中广泛实施了通用肿瘤检测，但有关检测结果的数据仍然有限。本研究提供了预测值，将有助于临床医生在林奇综合征背景下评估异常结果，并为患者咨询提供帮助。
