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PAX6 is frequently expressed in ependymal tumours and associated with prognostic relevant subgroups
  1. Julian Tabasaran1,
  2. Martin Schuhmann2,3,4,
  3. Martin Ebinger5,
  4. Jürgen Honegger2,3,
  5. Mirjam Renovanz2,3,6,
  6. Jens Schittenhelm1,3
  1. 1Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Germany
  2. 2Department of Neurosurgery, Eberhard Karls University of Tuebingen, Baden-Württemberg, Germany
  3. 3Center for Neuro-Oncology, Comprehensive Cancer Center Tuebingen-Stuttgart, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Germany
  4. 4Division of Pediatric Neurosurgery, Department of Neurosurgery, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Germany
  5. 5Department Pediatric Hematology/Oncology, Children's University Hospital, Eberhard Karls University of Tuebingen, Tuebingen, Germany
  6. 6Interdisciplinary Division of Neuro-Oncology, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Germany
  1. Correspondence to Professor Jens Schittenhelm, Department of Neuropathology, Eberhard Karls Universitat Tubingen, Tubingen, Baden-Württemberg, Germany; jens.schittenhelm{at}med.uni-tuebingen.de

Abstract

Aims An ependymoma shows divergent morphological and molecular features depending on their location. The paired box 6 (PAX6) transcription factor is a putative tumour suppressor and drives cancer cells towards a stem cell-like state. A transcriptome study reported high PAX6 expression in ependymal tumours, but data on protein expression are lacking.

Methods We, therefore, analysed PAX6 expression by immunohistochemistry in 172 ependymoma samples and correlated its expression to histology, WHO grade, anatomical location and molecular subgroups.

Results Mean PAX6 nuclear expression in ependymoma was 27.5% (95% CI 23.3 to 31.7). PAX6 expression in subependymoma (mean: 5%) was significantly lower compared with myxopapillary (30%), WHO grade II (26%) and anaplastic ependymoma (35%). Supratentorial ependymomas also displayed significant lower PAX6 levels (15%) compared with spinal cord tumours (30%). Expression levels in YAP1-fused ependymoma (41%) were higher compared with REL-associated protein (RELA)-fusion positive tumours (17%), while PAX6 expression was similar in posterior fossa group A (33%) and B (29%) ependymomas. Kaplan-Meier analysis in RELA-fusion positive ependymomas and posterior fossa group B showed a significant better outcome for PAX6 at or above the cut-off of 19.45% compared with tumours with PAX6 below the cut-off.

Conclusions We demonstrate that PAX6 is frequently expressed in human ependymal tumours and immunohistochemistry may be helpful in determining prognostic relevant subgroups.

  • immunohistochemistry
  • brain neoplasms
  • neuropathology

Data availability statement

Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. The individual datasets generated during and/or analysed during the current study are not publicly available due to privacy of research participants but are available from the corresponding author on reasonable request.

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Data availability statement

Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. The individual datasets generated during and/or analysed during the current study are not publicly available due to privacy of research participants but are available from the corresponding author on reasonable request.

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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors All authors made substantial contributions to the study, that is, conception, design, sample acquisition, clinical data acquisition, data analysis, data interpretation and coordination of experiments and collaborations. JT and JS designed and coordinated the study, evaluated, analysed and interpreted the results. JS wrote the first draft of the manuscript, created figures and data table. JH, MS, MR and ME provided clinical data. All authors read, modified the manuscript and approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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