Morphological and Molecular Profiling of Pediatric Brain Stem Gliomas.
Michael A Arnold, Shaefali Shandilya, Susana Galli, J Keith Killian, Mark Raffeld, Maria Tsokos, Paul S Meltzer, Katherine E Warren, Martha M Quezado. National Institutes of Health, Bethesda, MD
Background: Each year, about 2200 children will be diagnosed with a brain tumor, with up to 15% of these tumors localized to the brain stem, where they are uniformly lethal with a variable but typically short survival time. The mean age at diagnosis for primary brain stem tumors is 7 to 9 years, with roughly equal distribution between the sexes. Brain stem gliomas are diffusely infiltrating lesions of both low to high grade morphology. Response to standard treatment, a combination of radiation and chemotherapy regimens, has been disappointing, with minimal if any impact on overall survival. Given the dismal prognosis of these lesions, new therapeutic targets need to be identified. Current research has focused on mechanisms which promote tumor survival by apoptosis resistance, and the identification of “brain tumor stem cells” as potential explanations for resistance to current therapies. Identification of “tumor stem cell” populations in various tumors may allow for their specific eradication with lasting remissions.
Design: We review the morphology of pediatric brain stem gliomas and probe these tumors for chromosomal aberrations by comparative genomic hybridization (CGH). Using immunohistochemistry, we assay brain stem gliomas for the expression of p53, EGFR and Nestin. We also analyze these tumors for mutations in B-RAF.
Results: Our study describes the demographics and clinical features of brain stem gliomas from 13 patients ranging in age at diagnosis from three to 13 years. The tumors we examined are morphologically heterogeneous. We identify many chromosomal aberrations in brain stem glioms by comparative genomic hybridization (CGH), and correlate these findings with the clinical behavior of these tumors. We demonstrate expression of p53, EGFR and the stem cell marker Nestin in a subset of brain stem gliomas. We report the absence of valine to glutamate mutations at residue 600 (V600E) of the B-RAF gene in our cohort of tumors.
Conclusions: Further molecular and immunohistochemical characterization is ongoing, and our findings may identify genetic alterations in these tumors that may represent the molecular hallmarks of these lesions, genetic markers of prognosis, and potential targets for future therapies.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 6, Monday Morning