Nine symptomatic NF1-associated juvenile pilocytic astrocytomas (JPA) were examined for cancer-related gene products in a study using immuno-histochemistry and Western blots at Washington University School of Medicine, St Louis, MO; and the Mayo Clinic, Rochester, MN. NF-1 associated JPA strongly expressed the antibody epitope PEN5, a marker of post-02A stage oligodendroglial cells, and showed no alterations in the protein expression profiles p53, p16, retinoblastoma (RB), epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), platelet-derived growth factor A (PDGF-A), and PDGF-Ra. The study supports a distinct molecular pathogenesis for NF1-associated JPA, which differs from the genetic changes seen with the more clinically aggressive and diffusely infiltrative, sporadic fibrillary astrocytomas. [1]

COMMENT. Grade I juvenile pilocytic astrocytoma (JPA) develops in 15% of children with neurofibromatosis 1 (NF1). The incidence of malignant progression in JPA is much lower than with sporadic fibrillary astrocytomas. The mean age at diagnosis of JPA is 4.5 years. Most are clinically benign, but some progress and cause visual loss and hypothalamic dysfunction. The above study attempts to explain why benign astrocytomas become malignant in NF1, a question further discussed in an editorial. [2]

Neurofibromin, the NF1 gene product, acts as a tumor suppressor protein. Mutation in the NF1 gene is associated with inadequate levels of neurofibromin, leading to increased cell proliferation. In NF1, tumors develop in patients with an additional mutation and a loss of heterozygosity. By studying proteins with expression profiles typical of fibrillary astrocytomas, Li and associates show that NF1-associated JPA tumors differ from their sporadic counterpart by exhibiting loss of neurofibromin expression, and demonstrate that gene expression profile abnormalities found in fibrillary astrocytomas are lacking in JPA. It is suggested that distinct genetic pathways in NF1 may produce subsets of astrocytomas.

Dysplastic and heterotopic neurons in focal cortical dysplasia. These cell types were differentiated by demonstrating a differential expression of glutamate and GABA-A receptor subunit mRNA in single immuno-histochemically labeled neurons, microdissected from human focal cortical dysplasia specimens removed during epilepsy surgery, at the Children’s Hospital of Philadelphia, PA [3]. Dysplastic and heterotopic neurons may be pharmacologically distinct and differ in their contribution to epileptogenesis in focal cortical dysplasia.