title: Prognostic marker analysis in pediatric intracranial ependymomas.
abstract: Histologic grading methods dependent upon H&E staining review have not been shown to reliably predict survival in children with intracranial ependymomas due to the subjectivity of the analytical methods. We hypothesized that the immunohistochemical detection of MIB-1, Tenascin C, CD34, VEGF, and CA IX may represent objective markers of post-operative survival (Progression Free and Overall Survival; PFS, OS) in these patients. Intracranial ependymomas from patients aged 22 years or less were studied. The original histologic grade was recorded, H&E sections were reviewed for vascular proliferation status, and immunohistochemistry was used to determine MIB-1, Tenascin C, CD34, VEGF, and CA IX status. Based upon the World Health Organization (WHO) grading system, 3 Grade I, 18 Grade II and 9 Grade III ependymomas were studied. Median follow-up time was 9.0 years; median PFS was, 6.1 years. Original WHO grade did not correlate with PFS or OS. Peri-necrotic CA IX localization correlated with PFS (Log rank = 0.0181) and OS (Log rank p = 0.0015). All patients with a CA IX ≤ 5 % total area localization were alive at last follow-up. Perinecrotic CA IX staining was also associated with vascular proliferation (p = 0.006), though not with VEGF expression score. MIB-1 labeling index (LI) correlated with OS (HR 1.06, 95 % CI 1.01, 1.12) and PFS (HR 1.08, 95 % CI 1.02, 1.14). MIB-1 LI and perinecrotic CA IX individually correlated with PFS. The effect of perinecrotic CA IX remained when grade was added to a Cox model predicting PFS. Immunodetection of CA IX and MIB-1 expression are predictive biomarkers for survival in children with posterior fossa ependymomas. These markers represent objective indicators of survival that supplement H&E grading alone.
authors.affiliation: Department of Pathology, Duke University School of Medicine, DUMC Box 3712, Durham, NC, 27710, USA, roger.mclendon@duke.edu.
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Eric
authors.initials: E
authors.lastname: Lipp
authors.forename: Diane
authors.initials: D
authors.lastname: Satterfield
authors.forename: Melissa
authors.initials: M
authors.lastname: Ehinger
authors.forename: Alan
authors.initials: A
authors.lastname: Austin
authors.forename: Debra
authors.initials: D
authors.lastname: Fleming
authors.forename: Kathryn
authors.initials: K
authors.lastname: Perkinson
authors.forename: Michaela
authors.initials: M
authors.lastname: Lefaivre
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wiener
authors.forename: Sri
authors.initials: S
authors.lastname: Gururangan
authors.forename: Herbert
authors.initials: H
authors.lastname: Fuchs
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Patrick
authors.initials: P
authors.lastname: Healy
mesh_terms: D000293:Adolescent; D000974:Antibodies, Antinuclear / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D011379:Prognosis; D012189:Retrospective Studies; D019063:Tenascin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C440408:MIB-1 antibody; D019063:Tenascin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases