Loss of H3K27me3 in meningiomas
Authors: Farshad Nassiri, Justin Z Wang, Olivia Singh, Shirin Karimi, Tatyana Dalcourt, Nazanin Ijad, Neda Pirouzmand, Ho-Keung Ng, Andrea Saladino, Bianca Pollo, Francesco Dimeco, Stephen Yip, Andrew Gao, Kenneth D Aldape, Gelareh Zadeh, Kenneth Aldape, Karolyn Au, Jill Barnholtz-Sloan, Felix Behling, Wenya (Linda) Bi, Priscilla Brastianos, Nicholas Butowski, Chaya Brodie, Aaron Cohen-Gadol, Marta Couce, Francesco Dimeco, Kate Drummond, Ian Dunn, Aaron Cohen-Gadol, Eva Galanis, Norbert Galldiks, Caterina Giannini, Roland Goldbrunner, Oliver Hanemann, Christel Herold-Mende, Craig Horbinski, Raymond Huang, Mohsen Javadpour, Michael Jenkinson, Christine Jungk, Timothy Kaufmann, Boris Krischek, Sylvia Kurz, Daniel Lachance, Christian Lafougere, Katrin Lamszus, Ian Lee, Tathiana Malta, Serge Makarenko, Christian Mawrin, Michael McDermott, Christopher Millward, Jennifer Moliterno-Gunel, Andrew Morokoff, Farshad Nassiri, H K Ng, Houtan Noushmehr, Arie Perry, Laila Poisson, Bianco Pollo, Aditya Ragunathan, David Raleigh, Mirjam Renovanz, Franz Ricklefs, Felix Sahm, Andrea Saladino, Antonio Santacroce, Thomas Santarius, Christian Schichor, Nils Schimdt, Jens Schittenhelm, Warren Selman, Helen Shih, Jim Snyder, Matja Snuderl, Andrew Sloan, Suganth Suppiah, Erik Sulman, Ghazaleh Tabatabai, Marcos Tatagiba, Marcos Timmer, Joerg-Christian Tonn, Andreas Von Deimling, Michael Vogelbaum, Tobias Walbert, Justin Wang, Patrick Wen, Manfred Westphal, Stephen Yip, Gelareh Zadeh
Journal: Neuro-Oncology (2021)

There is a critical need for objective and reliable biomarkers of outcome in meningiomas beyond WHO classification. Loss of H3K27me3 has been reported as a prognostically unfavorable alteration in meningiomas. We sought to independently evaluate the reproducibility and prognostic value of H3K27me3 loss by immunohistochemistry (IHC) in a multicenter study.IHC staining for H3K27me3 and analyses of whole slides from 181 meningiomas across three centers was performed. Staining was analyzed by dichotomization into loss and retained immunoreactivity, and using a 3-tiered scoring system in 151 cases with clear staining. Associations of grouping with outcome were performed using Kaplan-Meier survival estimates.A total of 21 of 151 tumors (13.9%) demonstrated complete loss of H3K27me3 staining in tumor with retained endothelial staining. Overall, loss of H3K27me3 portended a worse outcome with shorter times to recurrence in our cohort, particularly for WHO grade 2 tumors which were enriched in our study. There were no differences in recurrence-free survival (RFS) for WHO grade 3 patients with retained vs loss of H3K27me3. Scoring by a 3-tiered system did not add further insights into the prognostic value of this H3K27me3 loss. Overall, loss of H3K27me3 was not independently associated with RFS after controlling for WHO grade, extent of resection, sex, age, and recurrence status of tumor on multivariable Cox regression analysis.Loss of H3K27me3 identifies a subset of WHO grade 2 and possibly WHO grade 1 meningiomas with increased recurrence risk. Pooled analyses of a larger cohort of samples with standardized reporting of clinical definitions and staining patterns are warranted.