ArticleActa neuropathologica2025
MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma.
Article in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- The impact of international care networks on the clinical management of constitutional mismatch repair deficiency (CMMRD): a review of recent developments.Familial cancer · 2026Review
- A PMS2-deficient pediatric high-grade glioma with PI3K-pathway mutations and adjacent developmental venous anomaly suggestive of CMMRD.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Distinct mutational signature and clonal evolution in constitutional mismatch repair deficiency-associated high-grade gliomas.iScience · 2026Article
- Clinicopathologic, molecular and tumor immune microenvironment features of mismatch repair-deficient glioblastomas in Lynch syndrome: a multicenter study of 29 cases with therapeutic implications.Acta neuropathologica communications · 2026Article
- Pediatric high-grade gliomas in patients with neurofibromatosis type 1-A collaborative cohort study from the SIOPE HGG/DIPG working group.Neuro-oncology practice · 2026Article
- Primary and metastatic brain tumours in hereditary cancer syndromes: case reports with and literature review.Hereditary cancer in clinical practice · 2026Article
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- Relationship between MLH1, MSH2, MSH6, and PMS2 protein expression status and clinicopathological characteristics in colorectal cancer tissues.Frontiers in medicine · 2026Article
- Unveiling MMR deficiency in pediatric and AYA high-grade gliomas: insights from multiomic profiling.Journal of neuro-oncology · 2025Article
- Is there a role for impaired DNA mismatch repair system in the pathogenesis of ameloblastomas? A scoping review.Journal of oral biology and craniofacial researchReview
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Abstract
Pediatric high-grade glioma (pedHGG) can occur as first manifestation of cancer predisposition syndromes resulting from pathogenic germline variants in the DNA mismatch repair (MMR) genes MSH2, MSH6, MLH1, and PMS2. The aim of this study was to establish a generalized screening for Lynch syndrome and constitutional MMR deficiency (CMMRD) in pedHGG patients, as the detection of MMR deficiencies (MMRD) may enable the upfront therapeutic use of checkpoint inhibitors and identification of variant carriers in the patients' families. We prospectively enrolled 155 centrally reviewed primary pedHGG patients for MMR-immunohistochemistry (IHC) as part of the HIT-HGG-2013 trial protocol. MMR-IHC results were subsequently compared to independently collected germline sequencing data (whole exome sequencing or pan-cancer DNA panel next-generation sequencing) available in the HIT-HGG-2013, INFORM, and MNP2.0 trials. MMR-IHC could be successfully performed in 127/155 tumor tissues. The screening identified all present cases with Lynch syndrome or CMMRD (5.5%). In addition, MMR-IHC also detected cases with exclusive somatic MMR gene alterations (2.3%), including MSH2 hypermethylation as an alternative epigenetic silencing mechanism. Most of the identified pedHGG MMRD patients had no family history of MMRD, and thus, they represented index patients in their families. Cases with regular protein expression in MMR-IHC never showed evidence for MMRD in DNA sequencing. In conclusion, MMR-IHC presents a cost-effective, relatively widely available, and fast screening method for germline MMRD in pedHGG with high sensitivity (100%) and specificity (96%). Given the relatively high prevalence of previously undetected MMRD cases among pedHGG patients, we strongly recommend incorporating MMR-IHC into routine diagnostics.
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