Low level of microsatellite instability in paediatric malignant astrocytomas.
OBJECTIVE
Microsatellite instability (MSI) has been proposed as a possible mechanism in the development of cancer. The aim of the current study was to determine whether MSI is involved in the pathogenesis of paediatric malignant astrocytomas.


METHODS
We screened a cohort of 126 high-grade astrocytoma samples for MSI using a sensitive and precise method of DNA analysis including a panel of five mononucleotide repeats, in combination with immunohistochemistry for DNA mismatch repair (MMR) proteins.


RESULTS
We identified low level of MSI (MSI-L) in four of 126 (3.2%) paediatric malignant astrocytic tumours. To analyse the molecular profile associated with MSI-L positive tumours, we performed immunohistochemistry for protein expression of hMSH6 and p53 as well as mutational analysis of the K-ras gene. In MSI-L paediatric malignant astrocytic tumours we detected retained nuclear expression of hMSH6 protein and strong nuclear accumulation of p53 protein indicating possible mutations of TP53. There was no correlation between K-ras mutational status and frequency of MSI in this patient population.


CONCLUSIONS
Our results suggest that the MSI-L phenotype is associated with p53 accumulation and/or mutations. However, this represents only a small subgroup of paediatric gliomas with possible distinct biological features, and the deficiencies of DNA MMR genes do not play a main role in the tumourigenesis of the majority of paediatric malignant astrocytomas.
Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany. valentina.vladimirova@ukb.uni-bonn.de
V
V
Vladimirova
D
D
Denkhaus
N
N
Soerensen
S
S
Wagner
J E A
JE
Wolff
T
T
Pietsch
D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D016159:Tumor Suppressor Protein p53