Portal de Periódicos da CAPES

Loss of H3K27me3 in meningiomas

2021; Oxford University Press; Volume: 23; Issue: 8 Linguagem: Inglês

10.1093/neuonc/noab036

1523-5866

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 Aldape, Gelareh Zadeh, Kenneth Aldape, Karolyn Au, Jill S. Barnholtz‐Sloan, Felix Behling, Wenya Linda Bi, Priscilla K. Brastianos, Nicholas Butowski, Chaya Brodie, Aaron Cohen‐Gadol, Marta Couce, Francesco DiMeco, Katharine J. Drummond, Ian F. Dunn, Aaron Cohen‐Gadol, E. Galanis, Norbert Galldiks, Caterina Giannini, Roland Goldbrunner, Oliver Hanemann, Christel Herold‐Mende, Craig Horbinski, Raymond Y. Huang, Mohsen Javadpour, Michael D. Jenkinson, Ho‐Keung Ng, Timothy J. Kaufmann, Boris Krischek, Sylvia C. Kurz, Daniel H. Lachance, Christian la Fougère, Katrin Lamszus, Ian Lee, Tathiana Malta, Serge Makarenko, Christian Mawrin, Michael McDermott, Christopher P. Millward, Jennifer Moliterno-Gunel, Andrew Morokoff, Farshad Nassiri, Ho‐Keung Ng, Houtan Noushmehr, Arie Perry, Laila Poisson, Bianco Pollo, Aditya Ragunathan, David R. Raleigh, Mirjam Renovanz, Franz Ricklefs, Felix Sahm, Andrea Saladino, Antonio Santacroce, Thomas Santarius, Christian Schichor, Nils Schimdt, Jens Schittenhelm, Warren R. Selman, Helen A. Shih, Jim Snyder, Matja Snuderl, Andrew Sloan, Suganth Suppiah, Erik P. Sulman, Ghazaleh Tabatabai, Marcos Tatagiba, Marcos Timmer, Joerg‐Christian Tonn, Andreas von Deimling, Michael A. Vogelbaum, Tobias Walbert, Justin Z. Wang, Patrick Y. Wen, Manfred Westphal, Stephen Yip, Gelareh Zadeh,

Glioma Diagnosis and Treatment

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.