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Diffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers

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Abstract

Diffusely infiltrating astrocytomas include diffuse astrocytomas WHO grade II and anaplastic astrocytomas WHO grade III and are classified under astrocytic tumours according to the current WHO Classification. Although the patients generally have longer survival as compared to those with glioblastoma, the timing of inevitable malignant progression ultimately determines the prognosis. Recent advances in molecular genetics have uncovered that histopathologically diagnosed astrocytomas may consist of two genetically different groups of tumours. The majority of diffusely infiltrating astrocytomas regardless of WHO grade have concurrent mutations of IDH1 or IDH2, TP53 and ATRX. Among these astrocytomas, no other genetic markers that may distinguish grade II and grade III tumours have been identified. Those astrocytomas without IDH mutation tend to have a distinct genotype and a poor prognosis comparable to that of glioblastomas. On the other hand, diffuse astrocytomas that arise in children do not harbour IDH/TP53 mutations, but instead display mutations of BRAF or structural alterations involving MYB/MYBL1 or FGFR1. A molecular classification may thus help delineate diffusely infiltrating astrocytomas into distinct pathogenic and prognostic groups, which could aid in determining individualised therapeutic strategies.

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Acknowledgments

The authors thank Dr Kai Yamasaki for his invaluable assistance in data mining, Dr Oltea Sampetrean for her valuable comments on the origin of gliomas, Drs Hiromichi Suzuki and Atsushi Natsume for sharing the information of their accepted manuscript and Dr Sylvia Kocialkowski for the critical reading of the manuscript. The results presented in this review here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. CEH is funded by the Canadian Institutes of Health Research and the Canadian Cancer Society Research Institute.

Conflict of interest

KI has received research grant from SRL, travel support from MSD and speaker honoraria from Eisai, Astellas Pharma, Otsuka Pharma, Sanofi, Daiichi Sankyo, Chugai Pharma, and TEIJIN Pharma. YN has received speaker honoraria from Eisai, Otsuka Pharma, MSD and Chugai Pharma.

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Authors and Affiliations

  1. Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Koichi Ichimura

  2. Department of Neuro-Oncology/Neurosurgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Yoshitaka Narita

  3. Division of Pathology, The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada

    Cynthia E. Hawkins

  4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

    Cynthia E. Hawkins

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  1. Koichi Ichimura
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  2. Yoshitaka Narita
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Correspondence to Koichi Ichimura.

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Ichimura, K., Narita, Y. & Hawkins, C.E. Diffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers. Acta Neuropathol 129, 789–808 (2015). https://doi.org/10.1007/s00401-015-1439-7

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