Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas

Aims: While it is well known that pilocytic astrocytomas are clinically dis tinct from diffuse astrocytomas, few comprehensive studies have focused on their genetic differences. The aim of this study was to examine pilocytic a strocytomas for genetic alterations that are commonly seen in diffuse astro cytomas. Methods and results: By using molecular genetic and immunohistochemical tec hniques, we evaluated p16, p53, CDK4 and PTEN genes in 29 pilocytic astrocy tomas. Mutation screening of p53 and PTEN was performed by single strand co nformation polymorphism analysis followed by direct sequencing. Loss of het erozygosity (LOH) of p53, p16 and 10q23-25 loci was performed with microsat ellite markers and genomic microsatellite instability (MSI) was also screen ed. Protein expression of p16, p53, CDK4 and PTEN was examined by immunohis tochemistry. Five tumours were found to have single genetic alterations, wh ich included a p53 mutation, a PTEN mutation, MSI at a single microsatellit e marker of the p16 locus, and one single LOH at each p16 and 10q23 loci. P rotein expressions of p16, CDK4 and PTEN were detected in 73%, 61% and 38% of tumours, respectively Significantly and in sharp contrast to diffuse ast rocytomas, no pilocytic astrocytoma in our series stained for p53 protein. Conclusion: Pilocytic astrocytomas have neither MSI phenotype nor recurrent alterations of the p53 and p16 genes. However, altered expression of PTEN may be important in the genesis of pilocytic astrocytomas. We conclude that pilocytic astrocytomas are genetically distinct from diffuse astrocytomas. Lack of p53 mutation/immunostaining may serve as a diagnostic adjunct for differentiating pilocytic astrocytomas from diffuse astrocytomas in small n eurosurgical biopsies.