LABORATORY INVESTIGATION - HUMAN/ANIMAL TISSUE Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas Manila Antonelli • Francesca Romana Buttarelli • Antonietta Arcella • Sumihito Nobusawa • Vittoria Donofrio • Hiroko Oghaki • Felice Giangaspero Received: 6 October 2009 / Accepted: 25 January 2010 Ó Springer Science+Business Media, LLC. 2010 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 prog- nostic. 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 muta- tions (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 sig- nificance, (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 prog- nostic factors are needed. Keywords Pediatric high-grade glioma Á YKL-40 expression Á TP53 mutation Á p53 expression Á IDH1 mutation Introduction Pediatric high-grade gliomas (pHGGs) are less frequent than their adult counterparts, but they account for 15% of all pediatric brain tumors, and show high mortality and morbidity [1]. They are anaplastic astrocytoma (WHO grade III) or glioblastoma (WHO grade IV), which are histologically indistinguishable from their counterparts in adults. The WHO grading system does not make any dis- tinction between HGGs in children and in adults [2, 3]. In adults, there are two subtypes of glioblastomas, i.e. primary (de novo) glioblastomas and secondary glioblastomas which develop though progression from low-grade or anaplastic astrocytomas [4, 5]. Primary glioblastomas affect predominantly older patients (mean, 62 years) and frequently exhibit epidermal growth factor receptor M. Antonelli Á F. Giangaspero (&) Department of Experimental Medicine, Sapienza University, Rome, Italy e-mail: felice.giangaspero@uniroma1.it F. R. Buttarelli Department of Neurological Sciences, Sapienza University, Rome, Italy A. Arcella Á F. Giangaspero IRCCS Neuromed Pozzilli (Isernia), Pozzilli, Italy S. Nobusawa Á H. Oghaki Section of Molecular Pathology, International Agency for Research on Cancer (IARC), Lyon, France V. Donofrio Department of Pathology Ospedale Pausilipon, AORN Santobono-Pausilipon, Naples, Italy 123 J Neurooncol DOI 10.1007/s11060-010-0129-5