TY  - JOUR
AU  - Nassiri, Farshad
AU  - Wang, Justin Z
AU  - Singh, Olivia
AU  - Karimi, Shirin
AU  - Dalcourt, Tatyana
AU  - Ijad, Nazanin
AU  - Pirouzmand, Neda
AU  - Ng, Ho-Keung
AU  - Saladino, Andrea
AU  - Pollo, Bianca
AU  - Dimeco, Francesco
AU  - Yip, Stephen
AU  - Gao, Andrew
AU  - Aldape, Kenneth D
AU  - Zadeh, Gelareh
AU  - Aldape, Kenneth
AU  - Au, Karolyn
AU  - Barnholtz-Sloan, Jill
AU  - Behling, Felix
AU  - Bi, Wenya
AU  - Brastianos, Priscilla
AU  - Butowski, Nicholas
AU  - Brodie, Chaya
AU  - Cohen-Gadol, Aaron
AU  - Couce, Marta
AU  - Dimeco, Francesco
AU  - Drummond, Kate
AU  - Dunn, Ian
AU  - Cohen-Gadol, Aaron
AU  - Galanis, Eva
AU  - Galldiks, Norbert
AU  - Giannini, Caterina
AU  - Goldbrunner, Roland
AU  - Hanemann, Oliver
AU  - Herold-Mende, Christel
AU  - Horbinski, Craig
AU  - Huang, Raymond
AU  - Javadpour, Mohsen
AU  - Jenkinson, Michael
AU  - Jungk, Christine
AU  - Kaufmann, Timothy
AU  - Krischek, Boris
AU  - Kurz, Sylvia
AU  - Lachance, Daniel
AU  - Lafougere, Christian
AU  - Lamszus, Katrin
AU  - Lee, Ian
AU  - Malta, Tathiana
AU  - Makarenko, Serge
AU  - Mawrin, Christian
AU  - McDermott, Michael
AU  - Millward, Christopher
AU  - Moliterno-Gunel, Jennifer
AU  - Morokoff, Andrew
AU  - Nassiri, Farshad
AU  - Ng, H. K.
AU  - Noushmehr, Houtan
AU  - Perry, Arie
AU  - Poisson, Laila
AU  - Pollo, Bianco
AU  - Ragunathan, Aditya
AU  - Raleigh, David
AU  - Renovanz, Mirjam
AU  - Ricklefs, Franz
AU  - Sahm, Felix
AU  - Saladino, Andrea
AU  - Santacroce, Antonio
AU  - Santarius, Thomas
AU  - Schichor, Christian
AU  - Schimdt, Nils
AU  - Schittenhelm, Jens
AU  - Selman, Warren
AU  - Shih, Helen
AU  - Snyder, Jim
AU  - Snuderl, Matja
AU  - Sloan, Andrew
AU  - Suppiah, Suganth
AU  - Sulman, Erik
AU  - Tabatabai, Ghazaleh
AU  - Tatagiba, Marcos
AU  - Timmer, Marcos
AU  - Tonn, Joerg-Christian
AU  - Von Deimling, Andreas
AU  - Vogelbaum, Michael
AU  - Walbert, Tobias
AU  - Wang, Justin
AU  - Wen, Patrick
AU  - Westphal, Manfred
AU  - Yip, Stephen
AU  - Zadeh, Gelareh
TI  - Loss of H3K27me3 in meningiomas
JO  - Neuro-Oncology
VL  - 23
IS  - 8
SN  - 1523-5866
CY  - Oxford
PB  - Oxford Univ. Press
M1  - FZJ-2021-03168
SP  - 1282 - 1291
PY  - 2021
AB  - BackgroundThere 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.MethodsIHC 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.ResultsA 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.ConclusionsLoss 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:33970242
UR  - <Go to ISI:>//WOS:000685248000012
DO  - DOI:10.1093/neuonc/noab036
UR  - https://juser.fz-juelich.de/record/894308
ER  -