Abstract
We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase IIβ (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population. We divided 124 medulloblastomas into three groups (NM−/GFAP−, NM +/GFAP−, and GFAP +) based on their immunoreactivity (IR) against NM and GFAP. The relationship among GLI3, NM, GFAP, and TOP2β was evaluated using fluorescent immunostaining and a publicly available single-cell RNA sequencing dataset. In total, 87, 30, and 7 medulloblastomas were classified as NM−/GFAP−, NM + /GFAP−, and GFAP +, and showed intermediate, good, and poor prognoses, respectively. GLI3-IR was frequently observed in NM +/GFAP− and GFAP + , and TOP2β-IR was frequently observed only in NM +/GFAP− medulloblastomas. In fluorescent immunostaining, TOP2β-IR was mostly co-localized with NeuN-IR but not with GFAP-IR. In single-cell RNA sequencing, TOP2β expression was elevated in CMAS/DCX-positive, but not in GFAP-positive, cells. NM-IR and GFAP-IR are important for estimating the prognosis of patients with medulloblastoma; hence they should be assessed in clinical practice.
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Acknowledgements
This research was supported by AMED under Grant Numbers JP18dm0107105 (M. Yoshida) and JP16kk0205009 (M. Yoshida). This work was also supported by Grants-in Aid from the Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants, the Ministry of Health, Labour and Welfare, Japan (K. Nakashima). The authors thank Satoshi Nakata for advices and support regarding statistical analyses using a publicly available genetic dataset of medulloblastomas.
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This study was conducted in line with the principles of the Declaration of Helsinki. Approvals were obtained from the institutional review boards of Aichi Medical University (#2020–005), Oita University (#1198), and joint-research faculties. The requirement for informed consent was waived owing to the retrospective nature of the study.
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Miyahara, H., Natsumeda, M., Kanemura, Y. et al. Topoisomerase IIβ immunoreactivity (IR) co-localizes with neuronal marker-IR but not glial fibrillary acidic protein-IR in GLI3-positive medulloblastomas: an immunohistochemical analysis of 124 medulloblastomas from the Japan Children’s Cancer Group. Brain Tumor Pathol 38, 109–121 (2021). https://doi.org/10.1007/s10014-021-00396-0
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DOI: https://doi.org/10.1007/s10014-021-00396-0