Prognostic significance of histological grading,p53 status,YKL-40 expression,and <Emphasis Type="Italic">IDH1</Emphasis> mutations in pediatric high-grade gliomas |
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Authors: | Manila Antonelli Francesca Romana Buttarelli Antonietta Arcella Sumihito Nobusawa Vittoria Donofrio Hiroko Oghaki Felice Giangaspero |
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Affiliation: | (1) Department of Experimental Medicine, Sapienza University, Rome, Italy;(2) Department of Neurological Sciences, Sapienza University, Rome, Italy;(3) IRCCS Neuromed Pozzilli (Isernia), Pozzilli, Italy;(4) Section of Molecular Pathology, International Agency for Research on Cancer (IARC), Lyon, France;(5) Department of Pathology Ospedale Pausilipon, AORN Santobono-Pausilipon, Naples, Italy; |
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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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