title: Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas.
abstract: The objective of this study was to evaluate, in a series of 43 pediatric high-grade gliomas (21 anaplastic astrocytoma WHO grade III and 22 glioblastoma WHO grade IV), the prognostic value of histological grading and expression of p53 and YKL-40. Moreover, mutational screening for TP53 and IDH1 was performed in 27 of 43 cases. The prognostic stratification for histological grading showed no difference in overall (OS) and progression-free survival (PFS) between glioblastomas and anaplastic astrocytomas. Overexpression of YKL40 was detected in 25 of 43 (58%) cases, but YKL-40 expression was not prognostic in terms of OS and PFS. p53 protein expression was observed in 13 of 43 (31%) cases but was not prognostic. TP53 mutations were detected in five of 27 (18%) cases (four glioblastomas and one anaplastic astrocytoma). Patients with TP53 mutation had a shorter median OS (9 months) and PFS (8 months) than those without mutations (OS, 17 months; PFS, 16 months), although this trend did not reach statistical significance (p = 0.07). IDH1 mutations were not detected in any of the cases analyzed. Our results suggest that in pediatric high-grade gliomas: (i) histological grading does not have strong prognostic significance, (ii) YKL-40 overexpression is less frequent than adult high-grade gliomas and does not correlate with a more aggressive behavior, (iii) TP53 mutations but not p53 expression may correlate with a more aggressive behavior, and (iv) IDH1 mutations are absent. These observations support the concept that, despite identical histological features, the biology of high-grade gliomas in children differs from that in adults, and therefore different prognostic factors are needed.
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome, Italy. felice.giangaspero@uniroma1.it
authors.forename: Manila
authors.initials: M
authors.lastname: Antonelli
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Buttarelli
authors.forename: Antonietta
authors.initials: A
authors.lastname: Arcella
authors.forename: Sumihito
authors.initials: S
authors.lastname: Nobusawa
authors.forename: Vittoria
authors.initials: V
authors.lastname: Donofrio
authors.forename: Hiroko
authors.initials: H
authors.lastname: Oghaki
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
mesh_terms: D054392:Adipokines; D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D000071451:Chitinase-3-Like Protein 1; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D004273:DNA, Neoplasm; D006023:Glycoproteins; D037102:Lectins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human