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. 2007 Apr;17(2):146-50.
doi: 10.1111/j.1750-3639.2007.00049.x.

Microsatellite instability in pediatric and adult high-grade gliomas

Anika Eckert  1 , Matthias Kloor, Antje Giersch, Rezvan Ahmadi, Christel Herold-Mende, Jürgen A Hampl, Frank L Heppner, Saida Zoubaa, Elke Holinski-Feder, Torsten Pietsch, Otmar D Wiestler, Magnus von Knebel Doeberitz, Wilfried Roth, Johannes Gebert
Affiliations

Microsatellite instability in pediatric and adult high-grade gliomas

Anika Eckert et al. Brain Pathol. 2007 Apr.

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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Figures

Figure 1
Figure 1
MSI analysis and MMR protein immunohistochemistry. A. MSI Analysis. The allele pattern of three mononucleotide markers (BAT25, BAT26, CAT25 in normal and tumor tissue are shown. Deleted nucleotides are depicted by arrows and indicate microsatellite instability in all three markers in the tumor tissue compared with the control tissue. B. Immunohistochemical staining of the MSI tumor. MMR proteins MLH1 and PMS2 are expressed regularly in tumor cell nuclei (brown) whereas loss of expression of MSH2 and MSH6 is indicated by absence of staining in tumor cells (blue nuclei). Endothelial cells express normal levels of these two proteins and served as internal controls.
See this image and copyright information in PMC

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