Pathological-Clinical Evaluation of High-Grade Gliomas in Children with Neurofibromatosis Type I
AJ Huttner, L Cruz, J Ladner, J Longtine, K Quayle, L Goumnerova, M Irons, M Kieran, N Ullrich. Yale University - Medical School, New Haven, CT; Brigham and Womens's Hospital, Harvard University - Medical School, Boston, MA; Children's Hospital, Harvard University - Medical School, Boston, MA
Background: Although Neurofibromatosis Type 1 (NF1) is one of the most frequent autosomal dominant disorders characterized by tumors of the central and peripheral nervous system, only very few pathologic studies analyze high grade gliomas in this group of patients. The gene product of the NF1 gene, neurofibromin, is an important regulator of cell proliferation and differentiation through negative interaction with the ras protein. Patients with NF1 are at increased risk of developing high grade malignant gliomas and glioblastomas, which are rare tumors in children and even less frequently observed in children with NF1. The objective of this study was to provide a clinicopathologic and molecular characterization of high grade gliomas in children with Neurofibromatosis Type I, and to determine whether specific pathologic or molecular features predict clinical behavior.
Design: We performed a retrospective review of patients with NF1 and high grade gliomas at the Childrens Hospital in Boston, which included the analysis of clinical records and pathological materials. Only patients who satisfied established current clinical criteria for NF1 and for whom pathologic material was available were included.
Results: A total of 6 patients were identified with NF1 and high grade gliomas. Clinical data demonstrate an average overall survival time of 5.2 years. The evaluation of H&E and immunohistochemical stains revealed highly pleomorphic GFAP-positive tumor cells with frequent mitoses in addition to necrosis and vascular proliferation. Molecular analyses displayed amplification of epidermal growth factor receptor copy numbers (EGFR-CISH), normal copy numbers for PTEN (PTEN-CISH), and hypomethylation of the MGMT locus.
Conclusions: This study provides preliminary evidence that children with NF1 develop high grade gliomas with unfavorable histological and molecular features, however, these patients have an overall increased survival time compared to children without NF1. These tumors will be studied with additional genomics/proteomics approaches to elicit molecular signatures unique for high grade gliomas in children with NF1.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 185, Tuesday Morning