Mitric Cristina, Salman Lina, Abrahamyan Lusine, Kim Soyoun Rachel, Pechlivanoglou Petros, Chan Kelvin K W, Gien Lilian T, Ferguson Sarah E
Division of Gynecologic Oncology, University Health Network and Sinai Health System, Toronto, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, Canada; Division of Gynecologic Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.
Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Gynecol Oncol. 2023 Mar;170:133-142. doi: 10.1016/j.ygyno.2022.12.008. Epub 2023 Jan 20.
Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but knowledge is limited on its value in epithelial ovarian cancer (EOC). The primary objective was to evaluate the prevalence of mismatch repair protein deficiency (MMRd), microsatellite instability (MSI)-high, and Lynch syndrome (LS) in epithelial ovarian cancer (EOC), as well as the diagnostic accuracy of LS screening tests. The secondary objective was to determine the prevalence of MMRd, MSI-high, and LS in synchronous ovarian endometrial cancer and in histological subtypes.
We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, and Embase databases. We included studies analysing MMR, MSI, and/or LS by sequencing.
A total of 55 studies were included. The prevalence of MMRd, MSI-high, and LS in EOC was 6% (95% confidence interval (CI) 5-8%), 13% (95% CI 12-15%), and 2% (95% CI 1-3%) respectively. Hypermethylation was present in 76% of patients with MLH1 deficiency (95% CI 64-84%). The MMRd prevalence was highest in endometrioid (12%) followed by non-serous non-mucinous (9%) and lowest in serous (1%) histological subtypes. MSI-high prevalence was highest in endometrioid (12%) and non-serous non-mucinous (12%) and lowest in serous (9%) histological subtypes. Synchronous and endometrioid EOC had the highest prevalence of LS pathogenic variants at 7% and 3% respectively, with serous having lowest prevalence (1%). Synchronous ovarian and endometrial cancers had highest rates of MMRd (28%) and MSI-high (28%). Sensitivity was highest for IHC (91.1%) and IHC with MSI (92.8%), while specificity was highest for IHC with methylation (92.3%).
MMRd and germline LS testing should be considered for non-serous non-mucinous EOC, particularly for endometrioid.
The rates of mismatch repair deficiency, microsatellite instability high, and mismatch repair germline mutations are highest in endometrioid subtype and non-serous non-mucinous ovarian cancer. The rates are lowest in serous histologic subtype.
在子宫内膜癌中，检测错配修复蛋白缺陷（MMRd）、微卫星不稳定性（MSI）和林奇综合征（LS）已被广泛接受，但关于其在上皮性卵巢癌（EOC）中的价值，相关认知有限。主要目的是评估上皮性卵巢癌（EOC）中错配修复蛋白缺陷（MMRd）、微卫星高度不稳定（MSI-high）和林奇综合征（LS）的患病率，以及LS筛查试验的诊断准确性。次要目的是确定同步性卵巢子宫内膜癌以及组织学亚型中MMRd、MSI-high和LS的患病率。
我们系统检索了MEDLINE、印刷版之前的Epub、MEDLINE在研及其他未索引引文、Cochrane对照试验中心注册库和Embase数据库。我们纳入了通过测序分析MMR、MSI和/或LS的研究。
共纳入55项研究。EOC中MMRd、MSI-high和LS的患病率分别为6%（95%置信区间（CI）5-8%）、13%（95%CI 12-15%）和2%（95%CI 1-3%）。76%的MLH1缺陷患者存在高甲基化（95%CI 64-84%）。MMRd患病率在子宫内膜样型中最高（12%），其次是非浆液性非黏液性型（9%），在浆液性组织学亚型中最低（1%）。MSI-high患病率在子宫内膜样型中最高（12%）和非浆液性非黏液性型中最高（12%），在浆液性组织学亚型中最低（9%）。同步性和子宫内膜样型EOC中LS致病变异的患病率最高，分别为7%和3%，浆液性亚型中患病率最低（1%）。同步性卵巢和子宫内膜癌中MMRd（28%）和MSI-high（28%）的发生率最高。免疫组化（IHC）（91.1%）和联合MSI的IHC（92.8%）敏感性最高，联合甲基化的IHC特异性最高（92.3%）。
对于非浆液性非黏液性EOC，尤其是子宫内膜样型，应考虑进行MMRd和胚系LS检测。
错配修复缺陷、微卫星高度不稳定和错配修复胚系突变率在子宫内膜样型和非浆液性非黏液性卵巢癌中最高。在浆液性组织学亚型中这些率最低。
