Low frequency of replication errors in primary nervous system tumours

Objectives-Automated DNA technology was used to analyze the incidence of mi crosatellite instability (MIN) among the most frequent types of adult prima ry CNS tumours and to determine its relation with clinicopathological chara cteristics. Methods-Fifty six gliomas, 32 meningiomas and 11 schwannomas were screened for size changes at eight microsatellite loci using fluorescent polymerase chain reaction (PCR) followed by fragment analysis in an automated sequence r. A tumour was considered as MIN+ when a different electrophoretic pattern between constitutional and tumour DNA was evidenced in one or more microsa tellite markers and as replication error positive (RER+) when at least 25% of the markers analyzed (2/8) showed instability. The MIN phenotype was cor related with relevant clinical and pathological parameters. Results-Globally, instability was found in 19/767 analyses (2.47%), with a higher rate among tetranuceotide than dinucleotide repeats (chi(2) test, p= 0.018). Ten gliomas (17.9%), two meningiomas (6.3%), and two schwannomas (1 8.2%) were MIN+, whereas one glioma (1.8%), two meningiomas (6.3%), and one schwannoma (9.1%) were classified as RER+. A possible association between microsatellite instability and a shorter duration of clinical course was fo und in meningiomas. The MIN+ phenotype was more frequent in spinal than int racranial schwannomas (Fisher's exact test, p=0.018). No other significant association with clinical or histological features was detected. Conclusions-Although microsatellite instability can be demonstrated at a lo w rate in some primary CNS tumours, a true replication error phenotype (rev ealed by widespread microsatellite instability at numerous loci) is uncommo n and unlikely to play an important part in the pathogenesis of these neopl asms. This form of instability was more frequent in tetranucleotide than in dinucleotide repeats. To our knowledge, this is the first report of MIN in schwannomas, where it was associated with the spinal localisation of the t umour.