EPM2 AIP1 immunohistochemistry as a surrogate of promoter methylation analysis in endometrial carcinoma.

IF 3.1 3区 医学 Q1 PATHOLOGY
Sonia Gatius, Marta Vaquero, Oliver Scheiber, Ana Velasco, Dolors Cuevas, Karl Kashofer, Maria Santacana, Núria Eritja, Sigurd Lax, Xavier Matias-Guiu
{"title":"EPM2 AIP1 immunohistochemistry as a surrogate of promoter methylation analysis in endometrial carcinoma.","authors":"Sonia Gatius, Marta Vaquero, Oliver Scheiber, Ana Velasco, Dolors Cuevas, Karl Kashofer, Maria Santacana, Núria Eritja, Sigurd Lax, Xavier Matias-Guiu","doi":"10.1007/s00428-025-04132-3","DOIUrl":null,"url":null,"abstract":"<p><p>Mismatch repair (MMR) status in endometrial carcinoma (EC) is crucial for diagnosis, prognosis, treatment, and Lynch syndrome pre-screening. MLH1 loss is the most frequent cause of MMR deficiency and usually by promoter hypermethylation. We tried to confirm the role of EPM2 AIP1 immunohistochemistry as a surrogate of MLH1 promoter methylation in EC. Case series from two different institutions were analyzed by comparable methods using immunohistochemistry for MMR proteins and EPM2 AIP1, and pyrosequencing for MLH1 methylation. In the first series of 70 cases, concordance was 100%, after reassessing three cases with methylation scores close to cut-off, by tumor cell enrichment. In the second series of 29 MLH1-deficient ECs, concordance was 96.5%, while in the control group of 30 MMR-proficient EC, one MLH1-positive case was EPM2 AIP1-negative. EPM2 AIP1 immunoreactivity was qualitatively superior in curettages and biopsies compared to hysterectomy. We conclude that EPM2 AIP1 immunohistochemistry is a good surrogate for MLH1 promoter methylation analysis, cost-effective with short turnaround time, but needs attention regarding preanalytical handling, normal tissue contamination, or low tumor percentage.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virchows Archiv","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00428-025-04132-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Mismatch repair (MMR) status in endometrial carcinoma (EC) is crucial for diagnosis, prognosis, treatment, and Lynch syndrome pre-screening. MLH1 loss is the most frequent cause of MMR deficiency and usually by promoter hypermethylation. We tried to confirm the role of EPM2 AIP1 immunohistochemistry as a surrogate of MLH1 promoter methylation in EC. Case series from two different institutions were analyzed by comparable methods using immunohistochemistry for MMR proteins and EPM2 AIP1, and pyrosequencing for MLH1 methylation. In the first series of 70 cases, concordance was 100%, after reassessing three cases with methylation scores close to cut-off, by tumor cell enrichment. In the second series of 29 MLH1-deficient ECs, concordance was 96.5%, while in the control group of 30 MMR-proficient EC, one MLH1-positive case was EPM2 AIP1-negative. EPM2 AIP1 immunoreactivity was qualitatively superior in curettages and biopsies compared to hysterectomy. We conclude that EPM2 AIP1 immunohistochemistry is a good surrogate for MLH1 promoter methylation analysis, cost-effective with short turnaround time, but needs attention regarding preanalytical handling, normal tissue contamination, or low tumor percentage.

EPM2 AIP1免疫组化作为子宫内膜癌启动子甲基化分析的替代。
错配修复(MMR)状态对子宫内膜癌(EC)的诊断、预后、治疗和Lynch综合征的预筛查至关重要。MLH1缺失是MMR缺陷最常见的原因,通常由启动子超甲基化引起。我们试图证实EPM2 AIP1免疫组化作为MLH1启动子甲基化在EC中的替代作用。来自两个不同机构的病例序列通过比较的方法进行分析,使用免疫组织化学检测MMR蛋白和EPM2 AIP1,以及焦磷酸测序检测MLH1甲基化。在第一个系列的70例病例中,通过肿瘤细胞富集重新评估甲基化评分接近临界值的3例病例后,一致性为100%。在第二组29例mlh1缺陷EC中,一致性为96.5%,而在对照组30例mmr熟练EC中,mlh1阳性1例EPM2 aip1阴性。与子宫切除术相比,刮宫和活检的EPM2 AIP1免疫反应性在质量上优于子宫切除术。我们得出结论,EPM2 AIP1免疫组织化学是MLH1启动子甲基化分析的良好替代方法,成本效益高,周转时间短,但需要注意分析前处理,正常组织污染或低肿瘤百分比。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Virchows Archiv
Virchows Archiv 医学-病理学
CiteScore
7.40
自引率
2.90%
发文量
204
审稿时长
4-8 weeks
期刊介绍: Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信