Congenital glioblastoma: A clinicopathologic and genetic analysis

• Type of Material: Article
• Authors: Daniel Brat, Emory University; Bahig Shehata, Emory University; Amilcar A Castellano-Sanchez, Departments of Pathology and Laboratory Medicine; Cynthia Hawkins, The Hospital for Sick Children; Robert B Yost, Department of Pathology; Claudia Greco, University of California, Davis; Claire Mazewski, Emory University; Anna Janss, Emory University; Hiroko Ohgaki, International Agency for Research on Cancer; Arie Perry, Washington University School of Medicine
• Language: English
• Date: 2007-07-01
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2007 The Authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/j.1750-3639.2007.00071.x
• Title of Journal or Parent Work: BRAIN PATHOLOGY
• Volume: 17
• Issue: 3
• Start Page: 276
• End Page: 281
• Grant/Funding Information: Supported in part by US Public Health Service National Institutes of Health (NIH) awards NS42934 and NS053727.
• Keywords: Clinical Neurology; NEUROPATHOLOGY; Neurosciences; PROGNOSIS; Pathology; TUMOR; Science & Technology; EXPRESSION; Neurosciences & Neurology; MALIGNANT ASTROCYTOMAS; P53 MUTATIONS; AMPLIFICATION; DE-NOVO; OVEREXPRESSION; 9 NEWBORNS; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Pathology

Abstract

Congenital central nervous system (CNS) tumors are uncommon, accounting for 1% of all childhood brain tumors. They present clinically either at birth or within the first 3 months. Glioblastoma (GBM) only rarely occurs congenitally and has not been fully characterized. We examined clinicopathologic features and genetic alterations of six congenital GBMs. Tumors were seen by neuroimaging as large, complex cerebral hemispheric masses. All showed classic GBM histopathology, including diffuse infiltration, dense cellularity, GFAP-positivity, high mitotic activity, endothelial proliferation and pseudopalisading necrosis. Neurosurgical procedures and adjuvant therapies varied. Survivals ranged from 4 days to 7.5 years; two of the three long-term survivors received chemotherapy, whereas the three short-term survivors did not. Paraffin-embedded tissue sections were used for FISH analysis of EGFR, chromosomes 9p21 (p16/CDKN2A) and 10q (PTEN/DMBT1); sequencing of PTEN and TP53; and immunohistochemistry for EGFR and p53. We uncovered 10q deletions in two cases. No EGFR amplifications, 9p21 deletions, or mutations of TP53 or PTEN were noted; however, nuclear p53 immunoreactivity was strong in 5/6 cases. Tumors were either minimally immunoreactive (n = 3) or negative (n = 3) for EGFR. We conclude that congenital GBMs show highly variable survivals. They are genetically distinct from their adult counterparts and show a low frequency of known genetic alterations. Nonetheless, the strong nuclear expression of p53 in these and other pediatric GBMs could indicate that p53 dysregulation is important to tumorigenesis. © 2007 The Authors.