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Brain Tumor Pathology

, Volume 35, Issue 2, pp 81–89 | Cite as

Reclassification of 400 consecutive glioma cases based on the revised 2016WHO classification

  • Yojiro Akagi
  • Koji Yoshimoto
  • Nobuhiro Hata
  • Daisuke Kuga
  • Ryusuke Hatae
  • Takeo Amemiya
  • Yuhei Sangatsuda
  • Satoshi O. Suzuki
  • Toru Iwaki
  • Masahiro Mizoguchi
  • Koji Iihara
Original Article
  • 276 Downloads

Abstract

In this study, we reclassified 400 consecutive glioma cases including pediatric cases, using the revised 2016 WHO classification with samples collected from the Kyushu University Brain Tumor Bank. The IDH1/2, H3F3A, key genetic markers in the 2016 classification, were analyzed using high-resolution melting, with DNA extracted from frozen tissues. The 1p/19q codeletions were evaluated using a microsatellite-based loss of heterozygosity analysis, with 18 markers, to detect loss of the entire chromosome arm. In the integrated diagnosis, 29 oligodendroglioma cases and 28 anaplastic oligodendroglioma cases were diagnosed as “IDH-mutant and 1p/19q-codeleted,” while 2 oligodendroglioma cases and 5 anaplastic oligodendroglioma cases were diagnosed as not otherwise specified (NOS). These “NOS” cases were either IDH-mutants or 1p/19q-codeleted, although characteristic oligodendroglial features were evident histologically. Better overall survival of patients with oligodendroglioma correlated with the molecular characteristic of “IDH-mutant and 1p/19q-codeleted,” rather than the WHO grade. Eleven “glioblastoma, IDH-wild-type” cases were classified as “1p/19q-codeleted”, however, chromosome 10 loss was also detected in 10 out of 11 cases. The 2016 WHO criteria for glioma classification leads to better diagnosis of patients. However, there are technical pitfalls and problems to be solved in the molecular analysis of routine diagnostics.

Keywords

Glioma WHO Classification Molecular diagnosis IDH TERT 

Notes

Acknowledgements

We thank Ms. Fumie Doi for her technical assistance regarding genetic analysis. This study was supported by JSPS KAKENHI Grant Numbers 17K10868, 16K10779 and 17K16652.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–20CrossRefPubMedGoogle Scholar
  2. 2.
    Komori T (2017) The 2016 WHO Classification of Tumours of the Central nervous system: the major points of revision. Neurol Med Chir (Tokyo) 57:301–11CrossRefGoogle Scholar
  3. 3.
    Komori T (2017) Updated 2016 WHO classification of tumors of the CNS: turning the corner where molecule meets pathology. Brain Tumor Pathol 34:139–40CrossRefPubMedGoogle Scholar
  4. 4.
    Louis DN, von Deimling A, Cavenee WK (2016) Diffuse astrocytoma and oligodendroglial tumors—introduction. In: Louis DN, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, von Deimling A (eds) WHO classification of tumours of the central nervous system (Revised 4th edition). International Agency for Research on Cancer, Lyon, pp 60–9Google Scholar
  5. 5.
    Eckel-Passow JE, Lachance DH, Molinaro AM et al (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372:2499–508CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Suzuki H, Aoki K, Chiba K et al (2015) Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 47:458–68CrossRefPubMedGoogle Scholar
  7. 7.
    Hatae R, Hata N, Yoshimoto K et al (2016) Precise DETECTION of IDH1/2 and BRAF hotspot mutations in clinical glioma tissues by a differential calculus analysis of high-resolution melting data. PLoS One 11:e0160489CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hatae R, Hata N, Suzuki SO et al (2017) A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology. Neuropathology 37:191–199CrossRefPubMedGoogle Scholar
  9. 9.
    Yoshimoto K, Iwaki T, Inamura T et al (2002) Multiplexed analysis of post-PCR fluorescence-labeled microsatellite alleles and statistical evaluation of their imbalance in brain tumors. Jpn J Cancer Res 93:284–90CrossRefPubMedGoogle Scholar
  10. 10.
    Yoshimoto K, Hatae R, Sangatsuda Y et al (2017) Prevalence and clinicopathological features of H3.3 G34-mutant high-grade gliomas: a retrospective study of 411 consecutive glioma cases in a single institution. Brain Tumor Pathol 34:103–12CrossRefPubMedGoogle Scholar
  11. 11.
    Hata N, Yoshimoto K, Hatae R et al (2016) Deferred radiotherapy and upfront procarbazine-ACNU-vincristine administration for 1p19q codeleted oligodendroglial tumors are associated with favorable outcome without compromising patient performance, regardless of WHO grade. Onco Targets Ther 9:7123–7131CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    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 27:5874–5880CrossRefPubMedGoogle Scholar
  13. 13.
    Cairncross G, Wang M, Shaw E et al (2013) Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31:337–43CrossRefPubMedGoogle Scholar
  14. 14.
    van den Bent MJ, Brandes AA, Taphoorn MJ et al (2013) Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31:344–50CrossRefPubMedGoogle Scholar
  15. 15.
    van den Bent MJ, Weller M, Wen PY et al (2017) A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics. Neuro Oncol 19:614–24CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mizoguchi M, Kuga D, Guan Y et al (2011) Loss of heterozygosity analysis in malignant gliomas. Brain Tumor Pathol 28:191–196CrossRefPubMedGoogle Scholar
  17. 17.
    Woehrer A, Hainfellner JA (2015) Molecular diagnostics: techniques and recommendations for 1p/19q assessment. CNS Oncol 4:295–306CrossRefPubMedGoogle Scholar
  18. 18.
    Smith JS, Alderete B, Minn Y et al (1999) Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18:4144–4152CrossRefPubMedGoogle Scholar
  19. 19.
    Vogazianou AP, Chan R, Backlund LM et al (2010) Distinct patterns of 1p and 19q alterations identify subtypes of human gliomas that have different prognoses. Neuro Oncol 12:664–78CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Snuderl M, Eichler AF, Ligon KL et al (2009) Polysomy for chromosomes 1 and 19 predicts earlier recurrence in anaplastic oligodendrogliomas with concurrent 1p/19q loss. Clin Cancer Res 15:6430–6437CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kuga D, Mizoguchi M, Guan Y et al (2008) Prevalence of copy-number neutral LOH in glioblastomas revealed by genomewide analysis of laser-microdissected tissues. Neuro Oncol 10:995–1003CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Reifenberger G, Collins VP, Hartmann C et al (2016) Oligodendroglioma, IDH-mutanta and 1p/19q-codeleted. In: Louis DN, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, von Deimling A (eds) WHO Classification of Tumours of the Central Nervous System (Revised 4th edition). International Agency for Research on Cancer, Lyon, pp 60–9Google Scholar

Copyright information

© The Japan Society of Brain Tumor Pathology 2018

Authors and Affiliations

  • Yojiro Akagi
    • 1
  • Koji Yoshimoto
    • 1
  • Nobuhiro Hata
    • 1
  • Daisuke Kuga
    • 1
  • Ryusuke Hatae
    • 1
  • Takeo Amemiya
    • 1
  • Yuhei Sangatsuda
    • 1
  • Satoshi O. Suzuki
    • 2
  • Toru Iwaki
    • 2
  • Masahiro Mizoguchi
    • 3
  • Koji Iihara
    • 1
  1. 1.Department of Neurosurgery, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Neuropathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of NeurosurgeryKitakyushu Municipal Medical CenterKitakyushuJapan

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