Pilocytic astrocytoma (WHO grade I) is a circumscribed, slowly growing, benign
astrocytoma that most frequently develops in the cerebellar hemispheres and in midline structures and occurs predominantly in childhood and adolescence. In contrast to diffusely infiltrating
gliomas in adults (e.g.
grade II astrocytomas,
oligodendrogliomas), survival of patients with
pilocytic astrocytoma is excellent after surgical intervention. To search for potential molecular mechanisms underlying its benign
biologic behavior, we compared gene expression profiles of
pilocytic astrocytomas (8 cases) with those of normal cerebellum (4 cases), low-grade
astrocytomas (WHO grade II; 15 cases), and
oligodendrogliomas (WHO grade II; 17 cases) by
cDNA array analysis. A number of immune system-related genes such as HLA-DRalpha,
HLA-DPB1,
HLA-DQB1,
IgG3, IgGK, FCER1G, A2M, FCRN, IFI-56K, and DAP12 were upregulated in
pilocytic astrocytomas relative to normal cerebellum,
grade II astrocytomas, and
oligodendrogliomas. Genes expressed at higher levels in
pilocytic astrocytomas than in
grade II astrocytomas and
oligodendrogliomas include HLA-DRalpha,
HLA-DPA1,
HLA-DPB1,
HLA-DQB1, A2M, TIMP1, TIMP2, CDKN1A, and SOCS3 and those expressed at lower levels include EGFR and PDGFRA. Hierarchical clustering analysis using the entire set of 1176 genes distinguished
pilocytic astrocytomas from
grade II astrocytomas and
oligodendrogliomas. Clustering analysis using selected subgroups of genes based on their molecular functions revealed that immune system-related genes (75 genes) or cell adhesion, migration, and angiogenesis-related genes (69 genes) showed similar power to the entire gene set for separation of
pilocytic astrocytomas from diffusely infiltrating low-grade
gliomas. Immunohistochemistry revealed that HLA-DRalpha is expressed diffusely in neoplastic cells in
pilocytic astrocytomas, whereas in
oligodendrogliomas, expression was limited to scattered reactive astrocytes. These results suggest that gene expression profiles of
pilocytic astrocytomas differ significantly from those of diffusely infiltrating low-grade
gliomas and that their benign
biologic behavior may be related to upregulation of immune defense-associated genes.