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Molecular subgrouping of ependymoma across three anatomic sites and their prognostic implications

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Abstract

The 2021 WHO classification stratifies ependymoma (EPN) into nine molecular subgroups according to the anatomic locations which outperforms histological grading. We aimed at molecularly reclassifying 200 EPN using immunohistochemistry (IHC) and sequencing for ZFTA fusions in supratentorial (ST) EPN. Further, we assessed the utility of L1CAM, cyclinD1, and p65 markers in identifying ZFTA fusion. Demographic profiles, histologic features, molecular subgroups and clinical outcome were retrospectively analyzed. IHC for L1CAM, cyclinD1, p65, H3K27me3, and H3K27M and sequencing for ZFTA fusion were performed. ZFTA fusions were identified in 44.8% ST EPN. p65 displayed the highest specificity (93.8%), while L1CAM had the highest sensitivity (92.3%) in detecting ZFTA fusions. The negative predictive value approached 96.6% and sensitivity improved to 96.2% with combinatorial IHC (L1CAM, cyclinD1, p65). H3K27me3 loss (PF-A) was noted in 65% PF EPN. Our results provide evidence that a combination of two of three (L1CAM, p65, and cyclinD1) can be used as surrogate markers for predicting fusion. ZFTA fusion, and its surrogate markers in ST, and H3K27me3 and younger age (< 5 years) in PF showed significant correlation with PFS and OS on univariate and Kaplan–Meier analysis. On multivariate analysis, H3K27me3 loss and younger age group are associated with poor clinical outcome.

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Acknowledgements

The authors would like to acknowledge and thank Mr. Sandeep Kumar, PhD scholar, for his help in preparation of tissue microarrays.

Funding

This work was partially supported by the Department of Science and Technology, Science and Engineering Research Board (DST-SERB), India (Grant No. EMR/2017/004385).

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Authors and Affiliations

  1. Department of Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Dheeraj Chinnam

  2. Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Kirti Gupta, Aastha Saraswati & Bishan Dass Radotra

  3. Department of Community Medicine and School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Tanvi Kiran

  4. Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Pravin Salunke

  5. Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Renu Madan & Narendra Kumar

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  1. Dheeraj Chinnam
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  2. Kirti Gupta
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  4. Aastha Saraswati
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Contributions

DC: material preparation, data collection, analysis including statistics and manuscript writing. KG: study conception, data analysis, critical review of literature, and manuscript writing; TK: interpretation of results and statistical analysis; AS: planning and executing the experiments, data interpretation; PS: data collection, operative details and follow-up; RM and NK: follow-up data collection; BDR: interpretation of results and critical review of manuscript.

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Correspondence to Kirti Gupta.

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This study was in accordance with the ethical standards of the institutional research committee and was approved by the same. The study conforms to the Declaration of Helsinki’s ethical principles. Written informed consent was acquired from all human subjects.

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Chinnam, D., Gupta, K., Kiran, T. et al. Molecular subgrouping of ependymoma across three anatomic sites and their prognostic implications. Brain Tumor Pathol 39, 151–161 (2022). https://doi.org/10.1007/s10014-022-00429-2

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  • DOI: https://doi.org/10.1007/s10014-022-00429-2

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