Brain Tumor Pathology

, Volume 30, Issue 1, pp 1–7 | Cite as

Clinicopathological features of human brainstem gliomas

  • Hidehiro Oka
  • Satoshi Utsuki
  • Yoshinori Tanizaki
  • Hiroyuki Hagiwara
  • Yoshiteru Miyajima
  • Kimitoshi Sato
  • Mari Kusumi
  • Chihiro Kijima
  • Kiyotaka Fujii
Original Article

Abstract

We describe the clinicopathological features of 25 brainstem gliomas (BSGs). Twenty BSGs located in the pons and were all in children. Four BSGs located in the medulla oblongata were in 2 children and 2 adults. One (in a child) was located in the midbrain. Radiological findings on MR images were low-intensity on T1 weighted images and high-intensity on T2 weighted images. Mean survival when pontine glioma was treated by radiotherapy and/or use of temozolomide was 14 months, although 4 patients (3 cervicomedullary types and one focal type arising from midbrain) are alive. Follow up was from 5 months to 6 years. Histopathological features of 10 cases of the diffuse type were: 4 grade II astrocytomas, 4 grade III astrocytomas, and 2 glioblastomas. MIB-1 index was from 0.8 to 38 %. P53 was positive for 80 % of 15 tumors and there were no negative results. MGMT was positive in 60 % of 15 tumors and negative in 12.4 %. IDH1 was negative in 61.6 %. There was no positive result for IDH1 in this study. Thus, our histopathological results were indicative of high p53 immunoreactivity and no IDH1 immunoreactivity related to secondary malignant change.

Keywords

Astrocytoma Brainstem glioma IDH1 p53 MGMT 

Notes

Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (nos 19591700 and 19590365) and a Parent’s Association Grant from Kitasato University School of Medicine, Japan. We wish to thank Ms Yoshie Yasui for providing technical assistance.

References

  1. 1.
    Hargrave D, Bartels U, Bouffet E (2006) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7:241–248PubMedCrossRefGoogle Scholar
  2. 2.
    Guillamo JS, Monjour A, Taillandier L et al (2001) Brainstem gliomas in adults: prognostic factors and classification. Brain 124:2528–2539PubMedCrossRefGoogle Scholar
  3. 3.
    Leach PA, Estlin EJ, Coope DJ et al (2008) Diffuse brainstem gliomas in children: should we or shouldn’t we biopsy? Br J Neurosurg 22:619–624PubMedCrossRefGoogle Scholar
  4. 4.
    Puputti M, Tynninen O, Sihto H et al (2006) Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas. Mol Cancer Res 4:927–934PubMedCrossRefGoogle Scholar
  5. 5.
    Di Sapio A, Morra I, Pradotto M et al (2002) Molecular genetic changes in a series of neuroepithelial tumors of childhood. J Neurooncol 59:117–122PubMedCrossRefGoogle Scholar
  6. 6.
    Wong KK, Tsang YT, Chang YM et al (2006) Genome-wide allelic imbalance analysis of pediatric gliomas by single nucleotide polymorphic allele array. Cancer Res 66:11172–11178PubMedCrossRefGoogle Scholar
  7. 7.
    Sung T, Miller DC, Hayes RL et al (2000) Preferential inactivation of the p53 tumor suppressor pathway and lack of EGFR amplification distinguish de novo high grade pediatric astrocytomas from de novo adult astrocytomas. Brain Pathol 10:249–259PubMedCrossRefGoogle Scholar
  8. 8.
    Liang ML, Ma J, Ho M et al (2008) Tyrosine kinase expression in pediatric high-grade astrocytoma. J Neurooncol 87:247–253PubMedCrossRefGoogle Scholar
  9. 9.
    Cheng Y, Ng HK, Zhang SF et al (1999) Genetic alterations in pediatric high-grade astrocytomas. Hum Pathol 30:1284–1290PubMedCrossRefGoogle Scholar
  10. 10.
    Badhe PB, Chauhan PP, Mehta NK (2004) Brainstem gliomas—a clinicopathological study of 45 cases with p53 immunohistochemistry. Indian J Cancer 41:170–174PubMedGoogle Scholar
  11. 11.
    Louis DN, Rubio MP, Correa KM et al (1993) Molecular genetics of pediatric brain stem gliomas. Application of PCR techniques to small and archival brain tumor specimens. J Neuropathol Exp Neurol 52:507–515PubMedCrossRefGoogle Scholar
  12. 12.
    Zhang S, Feng X, Koga H et al (1993) p53 gene mutations in pontine gliomas of juvenile onset. Biochem Biophys Res Commun 196:851–857PubMedCrossRefGoogle Scholar
  13. 13.
    Sure U, Ruedi D, Tachibana O et al (1997) Determination of p53 mutations, EGFR overexpression, and loss of p16 expression in pediatric glioblastomas. J Neuropathol Exp Neurol 56:782–789PubMedGoogle Scholar
  14. 14.
    Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812PubMedCrossRefGoogle Scholar
  15. 15.
    Balss J, Meyer J, Mueller W et al (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602PubMedCrossRefGoogle Scholar
  16. 16.
    Bleeker FE, Lamba S, Leenstra S et al (2009) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30:7–11PubMedCrossRefGoogle Scholar
  17. 17.
    Hartmann C, Meyer J, Balss J et al (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118:469–474PubMedCrossRefGoogle Scholar
  18. 18.
    Sanson M, Marie Y, Paris S et al (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154PubMedCrossRefGoogle Scholar
  19. 19.
    Watanabe T, Nobusawa S, Kleihues P et al (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153PubMedCrossRefGoogle Scholar
  20. 20.
    Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773PubMedCrossRefGoogle Scholar
  21. 21.
    Ichimura K, Pearson DM, Kocialkowski S et al (2009) IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro-Oncol 11:341–347PubMedCrossRefGoogle Scholar
  22. 22.
    Nobusawa S, Watanabe T, Kleihues P et al (2009) IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15:6002–6007PubMedCrossRefGoogle Scholar
  23. 23.
    Thorarinsdottir HK, Santi M, McCarter R et al (2008) Protein expression of platelet-derived growth factor receptor correlates with malignant histology and PTEN with survival in childhood gliomas. Clin Cancer Res 14:3386–3394PubMedCrossRefGoogle Scholar
  24. 24.
    Nakamura M, Shimada K, Ishida E et al (2007) Molecular pathogenesis of pediatric astrocytic tumors. Neuro-Oncol 9:113–123PubMedCrossRefGoogle Scholar
  25. 25.
    Geoerger B, Morland B, Ndiaye A et al (2009) Target-driven exploratory study of imatinib mesylate in children with solid malignancies by the Innovative Therapies for Children with Cancer (ITCC) European Consortium. Eur J Cancer 45:2236–2238CrossRefGoogle Scholar
  26. 26.
    Wakabayashi T, Natsume A, Hatano H et al (2009) p16 promoter methylation in the serum as a basis for the molecular diagnosis of gliomas. Neurosurgery 64:455–461PubMedCrossRefGoogle Scholar
  27. 27.
    Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRefGoogle Scholar
  28. 28.
    van den Bent MJ, Dubbink HJ, Sanson M et al (2009) MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol 27:5881–5886PubMedCrossRefGoogle Scholar
  29. 29.
    Wick W, Hartmann C, Engel C et al (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27:5874–5880PubMedCrossRefGoogle Scholar

Copyright information

© The Japan Society of Brain Tumor Pathology 2012

Authors and Affiliations

  • Hidehiro Oka
    • 1
  • Satoshi Utsuki
    • 1
  • Yoshinori Tanizaki
    • 1
  • Hiroyuki Hagiwara
    • 1
  • Yoshiteru Miyajima
    • 1
  • Kimitoshi Sato
    • 1
  • Mari Kusumi
    • 1
  • Chihiro Kijima
    • 1
  • Kiyotaka Fujii
    • 1
  1. 1.Department of NeurosurgeryKitasato University School of MedicineSagamiharaJapan

Personalised recommendations