中国一项新诊断子宫内膜癌患者林奇综合征筛查策略的比较：前瞻性队列研究。

Comparison of screening strategies for Lynch syndrome in patients with newly diagnosed endometrial cancer: a prospective cohort study in China.

机构信息

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, P.R. China.

Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, P.R. China.

出版信息

Cancer Commun (Lond). 2019 Jul 15;39(1):42. doi: 10.1186/s40880-019-0388-2.

DOI:10.1186/s40880-019-0388-2

PMID:31307542

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6628486/

Abstract

BACKGROUND

The prevalence of Lynch syndrome and screening strategies for this disorder in Chinese patients with endometrial cancer have seldom been investigated. Such data would be essential for the screening, prevention, genetic counseling, and treatment of Lynch syndrome. The purpose of this prospective study was to determine the accuracy of the mismatch repair (MMR) protein immunohistochemistry (IHC), microsatellite instability (MSI) test, and clinical diagnostic criteria in screening for Lynch syndrome-associated endometrial cancer (LS-EC) in a prospective Chinese cohort.

METHODS

All patients with newly diagnosed endometrial cancer (EC) were evaluated using clinical diagnostic criteria (Amsterdam II criteria and the revised Bethesda guidelines), MSI test, and IHC of MMR proteins in tumor tissues. For all patients, the screening results were compared with results of germline sequencing for pathogenic variants of MMR genes.

RESULTS

Between December 2017 and August 2018, a total of 111 unselected patients with newly diagnosed EC were enrolled. Six patients (5.4%) harbored a pathogenic germline mutation of MMR genes: 1 had a mutation in MutL homolog 1 (MLH1), 2 in MutS homolog 2 (MSH2), and 3 in MutS homolog 6 (MSH6). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying LS-EC were 33.3%, 88.6%, 14.3%, and 95.9%, for the clinical criteria, 66.7%, 75.0%, 14.3%, and 97.3% for IHC of MMR proteins, 100%, 89.9%, 33.3%, and 100% for MSI test, and 100%, 72.4%, 20.0% and 100% for combined IHC and MSI test, respectively. The combination of IHC and MSI test had higher sensitivity and PPV than the clinical criteria (p = 0.030). MSI test and IHC were highly concordant for LS-EC screening (73/77, 94.8%).

CONCLUSION

The accuracy of the combination of IHC of MMR proteins and MSI test for screening LS among Chinese patients with EC was superior to that of the clinical criteria. Trial registration NCT03291106. Registered on September 25, 2017.

摘要

背景

林奇综合征（Lynch syndrome）在子宫内膜癌患者中的患病率及其筛查策略在中国鲜有研究。这些数据对于林奇综合征的筛查、预防、遗传咨询和治疗至关重要。本前瞻性研究旨在通过对中国人群进行前瞻性队列研究，评估错配修复（MMR）蛋白免疫组化（IHC）、微卫星不稳定性（MSI）检测和临床诊断标准在筛查林奇综合征相关子宫内膜癌（LS-EC）中的准确性。

方法

所有新诊断的子宫内膜癌（EC）患者均采用临床诊断标准（Amsterdam II 标准和修订的 Bethesda 指南）、MSI 检测和肿瘤组织中 MMR 蛋白的 IHC 进行评估。对所有患者，将筛查结果与 MMR 基因致病性变异的种系测序结果进行比较。

结果

2017 年 12 月至 2018 年 8 月，共纳入 111 例新诊断的 EC 患者。6 例（5.4%）患者携带 MMR 基因致病性种系突变：1 例 MLH1 突变，2 例 MSH2 突变，3 例 MSH6 突变。临床标准识别 LS-EC 的灵敏度、特异性、阳性预测值（PPV）和阴性预测值（NPV）分别为 33.3%、88.6%、14.3%和 95.9%，MMR 蛋白 IHC 分别为 66.7%、75.0%、14.3%和 97.3%，MSI 检测分别为 100%、89.9%、33.3%和 100%，联合 IHC 和 MSI 检测分别为 100%、72.4%、20.0%和 100%。与临床标准相比，联合 IHC 和 MSI 检测具有更高的灵敏度和 PPV（p=0.030）。MSI 检测和 IHC 对 LS-EC 筛查具有高度一致性（73/77，94.8%）。