Abstract #17

by | Sep 18, 2023 | 2023 Abstracts

Abstract 17- 0830-0845
Category: Clinical

At the end of the session, participants will be able to:

  1. Discuss molecular alterations that impact survival in grade 3 meningiomas.
  2. Illustrate immunohistochemical stains that may be used as potential surrogate markers for predicting molecular alterations in grade 3 meningiomas.

COI Disclosure:

None to disclose

Presenter

Karina Chornenka Martin is a PGY-4 Neuropathology Resident at the University of British Columbia.

Authors

Karina Chornenka Martin, MD1, Kira Tosefsky, BSc2, Alexander D. Rebchuk, MD MSc2, Justin Z. Wang, MD3,4,5, Gelareh Zadeh, MD PhD3,4,5, Serge Makarenko, MD2, Stephen Yip, MD PhD1

1 Department of Pathology & Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

2 Division of Neurosurgery, University of British Columbia, Vancouver, Canada

3 Division of Neurosurgery, University of Toronto, Toronto, Canada

4 MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada

5 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada

    Target Audience:

    Pathologists, Residents, Medical Students

    CanMEDS:
    Medical Expert (the integrating role), Communicator, Collaborator, Leader, Health Advocate, Scholar, Professional

    Using molecular and immunohistochemical features to predict outcomes in grade 3 meningiomas

    Abstract

    Objective: The WHO 2021 classification introduces molecular alterations in meningiomas that are associated with increased risk of recurrence and/or shortened overall survival (OS). These include TERT promoter (TERTp) mutations, CDKN2A/B homozygous deletion, H3 K27me3 loss, and BAP1 loss. With precise prognostic implications pending further characterization,  we explored these molecular alterations and associated clinical outcomes in a single-center cohort of grade 3 meningiomas. Furthermore, we examined whether MTAP and p16 immunohistochemistry can predict CDKN2A/B status. 

    Methods: Clinical and histopathological information were obtained from the electronic medical records of grade 3 meningiomas resected at a tertiary center between 2007-2020. Molecular testing for TERTp mutations and CDKN2A/B status, methylation profiling, and immunohistochemistry for H3 K27me3, BAP1, p16, and MTAP were performed. Predictors of survival were identified by Cox regression. MTAP and p16 expression were assessed and correlated with CDKN2A/B status. 

    Results: Out of 15 cases included in the study, 8/15 were classified as anaplastic, 6/15 as rhabdoid and 1/15 as papillary. One rhabdoid tumour exhibited BAP1 loss, four tumours harboured TERTp mutations and three demonstrated CDKN2A/B homozygous deletion. TERTp mutations and CDKN2A status were associated with significant reductions in OS, which was independent of Simpson resection grade. Meningiomas with CDKN2A/B homozygous deletion showed consistent loss of p16 and MTAP immunoreactivity. 

    Conclusion:  TERTp mutations and CDKN2A/B homozygous deletion are significantly associated with reduced OS independent of resection extent. Our findings support using these molecular markers for prognostication in meningiomas. Additionally, this small series demonstrates that p16 and MTAP immunohistochemistry can predict CDKN2A/B status.