Microsatellite Instability in Pediatric and Adult High-grade Gliomas

Overview

Journal Brain Pathol

Date 2007 Mar 29

PMID 17388945

Citations 24

Authors

Anika Eckert

Matthias Kloor

Antje Giersch

Rezvan Ahmadi

Christel Herold-Mende

Jurgen A Hampl

Frank L Heppner

Saida Zoubaa

Elke Holinski-Feder

Torsten Pietsch

Otmar D Wiestler

Magnus von Knebel Doeberitz

Wilfried Roth

Johannes Gebert

Affiliations

Soon will be listed here.

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.

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