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Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas

  • Laboratory Investigation - Human/Animal Tissue
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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.

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Acknowledgments

This study was in part supported by “Il Fondo di Giò Onlus”. Manila Antonelli is supported by a grant from Associazione Italiana per la Lotta al Neuroblastoma. We thank Maura Massimino and Maria Luisa Garrè for their assistance with the clinical information, and Alessandra Angiolosanto and Anne-Marie Camus for technical assistance.

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Authors and Affiliations

  1. Department of Experimental Medicine, Sapienza University, Rome, Italy

    Manila Antonelli & Felice Giangaspero

  2. Department of Neurological Sciences, Sapienza University, Rome, Italy

    Francesca Romana Buttarelli

  3. IRCCS Neuromed Pozzilli (Isernia), Pozzilli, Italy

    Antonietta Arcella & Felice Giangaspero

  4. Section of Molecular Pathology, International Agency for Research on Cancer (IARC), Lyon, France

    Sumihito Nobusawa & Hiroko Oghaki

  5. Department of Pathology Ospedale Pausilipon, AORN Santobono-Pausilipon, Naples, Italy

    Vittoria Donofrio

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  1. Manila Antonelli
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Correspondence to Felice Giangaspero.

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Antonelli, M., Buttarelli, F.R., Arcella, A. et al. Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas. J Neurooncol 99, 209–215 (2010). https://doi.org/10.1007/s11060-010-0129-5

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  • DOI: https://doi.org/10.1007/s11060-010-0129-5

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