临床与实验病理学杂志2026，Vol.42Issue(3)：342-351,10.DOI:10.13315/j.cnki.cjcep.2026.03.009
错配修复蛋白缺陷性胶质瘤的临床病理及分子遗传学特征
Clinicopathological and molecular genetic characteristics of mismatch repair protein-deficient gliomas
摘要
Abstract
Objective To analyze the clinicopathological and molecular genetic characteristics of mismatch re-pair protein-deficient(dMMR)gliomas.Methods Collect clinical data from 20 cases of dMMR glioma confirmed by pathological diagnosis and surgically resected.Mismatch repair(MMR)protein expression was evaluated by immuno-histochemistry,with genetic alterations confirmed via Sanger sequencing and next-generation sequencing(NGS).Re-sults All 20 dMMR gliomas were located supratentorially,with 2 cases presenting multiple lesions.Patient age ranged from 15 to 77 years;18 patients were over 40 years old.Cases included 5 recurrences and 15 newly diagnosed gliomas(hereditary and sporadic).Integrated diagnoses were:14 cases of glioblastoma(IDH wild type,WHO grade 4),4 cases of anaplastic astrocytoma(IDH mutant,WHO grade 4),1 case of anaplastic oligodendroglioma(IDH mu-tant with 1p/19q co-deletion,WHO grade 3),and 1 case of diffuse midline glioma(H3K27 alteration,WHO grade 4).Histological features:multinucleated tumor giant cells were observed in 16 cases(80%),all in glioblastoma and astrocytoma.Microvascular proliferation was present in 6 cases,with only 1 case exhibiting significant proliferation.MMR protein expression showed MLH1 and/or PMS2 loss in 9 cases,and MSH2 and/or MSH6 loss in 10 cases.One case with partial loss of MSH2 and MSH6 was confirmed to harbor an MSH2 mutation by NGS.Among the 8 cases sub-jected to NGS,molecular profiling revealed:microsatellite instability-high(MSI-H)in 25%(2/8),high tumor muta-tional burden(TMB-H)in 37.5%(3/8),TP53 mutations in 87.5%(7/8),NF1 mutations in 75%(6/8),and NOTCH1 mutations in 50%(4/8).Notably,the single Lynch syndrome-associated oligodendroglioma within this co-hort harbored concurrent IDH2 R172K,TP53,and NF1 mutations.The median overall survival for the dMMR glioma cohort was 9.5 months.Conclusion In high-grade gliomas,the presence of multinucleated giant cells,lymphocytic infiltration,multifocality,or recurrence should prompt dMMR evaluation.Pathologists should note partial loss of MMR proteins,and NGS and methylation profiling may be performed to further clarify the diagnosis when necessary.They commonly harbor TP53 and NF1 mutations,while genetic alterations such as EGFR amplification,PTEN muta-tions,and TERT promoter mutations are less frequently.关键词
胶质瘤/错配修复蛋白缺陷/病理学/免疫组织化学/基因检测Key words
glioma/mismatch repair protein/pathology/immunohistochemistry/genetic testing分类
医药卫生引用本文复制引用
周婧,杨树东,陈刚,韩雪,孙爱娟,潘敏鸿..错配修复蛋白缺陷性胶质瘤的临床病理及分子遗传学特征[J].临床与实验病理学杂志,2026,42(3):342-351,10.基金项目
无锡市人民医院2025"雁阵人才"学科带头人-2025(2025-YZ-XKDTR-YSD-2025) 2025"Wild Goose Array Talents"Discipline Leader Fund of Wuxi People's Hospital(2025-YZ-XKDTR-YSD-2025) （2025-YZ-XKDTR-YSD-2025）
