Pilocytic Astrocytomas of the Optic Nerve and Their Relation to Pilocytic Astrocytomas Elsewhere in the Central Nervous System
Gerald F Reis, Michele Bloomer, Anthony Karnezis, Joanna Phillips, Patricia Goldhoff, Tarik Tihan. University of California San Francisco, San Francisco, CA
Background: Pilocytic astrocytoma (PA) is an indolent neoplasm common in children. Total resection typically provides cure, but many PAs cannot be totally resected and require adjuvant treatment. PA of the optic nerve (a.k.a. optic glioma) is a subtype with more aggressive behavior. In most studies, these have been considered within a larger category of “optic pathway glioma” that included hypothalamic PAs. BRAF gene duplication and activation of downstream MEK/ERK has been recently reported in PA, but very few to no optic nerve tumors were evaluated. Our study reviews the clinicopathological and molecular features of optic nerve PAs to determine whether they can be distinguished from PAs located elsewhere in the central nervous system (CNS).
Design: We searched for optic PAs treated at the University of California Medical Center (UCSF) between 1954-2010. In addition, we utilized data from a recent multi-institutional study of intracranial PA for comparison. Clinical information was obtained from medical records, and cases were selected based on histologic diagnosis. We assessed BRAF duplication by immunohistochemistry and FISH. Immunohistochemistry included standard markers as well as p16, phospho-histone H2AX, and pERK.
Results: We identified 22 patients (16 male, 6 female) with optic nerve glioma. The median age of diagnosis was 9 years. All patients underwent surgery, and gross total resection was achieved in 15 cases. One patient received chemotherapy; none received radiation. There were no deaths. When compared to intracranial PA, there was no statistical significance in terms of median age (P = 0.21). Post-surgical treatment was significantly different in terms of radiotherapy and chemotherapy. While the follow-up was longer and more complete for the intracranial group, differences in outcome were noted between the groups. Immunohistochemistry for BRAF was not useful in determining BRAF duplication, but FISH analysis showed that BRAF duplication was more frequent in posterior fossa PA (p<0.001). Staining for p16 was more frequently observed in tumors with BRAF duplication. H2AX staining was not useful in distinguishing among PA subtypes.
Conclusions: The strong correlation between BRAF duplication and pERK/p16 positivity suggests that the BRAF/p16 pathway is active in a subset of PAs and may be associated with oncogene-induced senescence. Our study further supports the increasing body of evidence suggesting that BRAF duplication is more typical of posterior fossa PA and is distinctly less common at other sites.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 257, Tuesday Afternoon