title: Microsatellite instability in pediatric and adult high-grade gliomas.
abstract: About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (approximately 25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms.
authors: Department of Applied Tumor Biology, University Hospital Heidelberg, Heidelberg, Germany.
authors: Anika
authors: A
authors: Eckert
authors: Matthias
authors: M
authors: Kloor
authors: Antje
authors: A
authors: Giersch
authors: Rezvan
authors: R
authors: Ahmadi
authors: Christel
authors: C
authors: Herold-Mende
authors: Jürgen A
authors: JA
authors: Hampl
authors: Frank L
authors: FL
authors: Heppner
authors: Saida
authors: S
authors: Zoubaa
authors: Elke
authors: E
authors: Holinski-Feder
authors: Torsten
authors: T
authors: Pietsch
authors: Otmar D
authors: OD
authors: Wiestler
authors: Magnus
authors: M
authors: von Knebel Doeberitz
authors: Wilfried
authors: W
authors: Roth
authors: Johannes
authors: J
authors: Gebert
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D004268:DNA-Binding Proteins / Q000378:metabolism; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D016133:Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins