Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence
2018
Epigenetic patterns on the level of
DNA methylationhave already been shown to separate clinically relevant subgroups of
meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232
meningiomasfrom 232 patients. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative. Finally, 13 cases yielded equivocal staining patterns. Reduced abundance of H3K27me3 in cases with staining limited to vessels was confirmed by mass spectrometry on a subset of cases. Lack of staining for H3K27me3 in all tumor cells was significantly associated with more rapid progression (p = 0.009). In line, H3K27me3-negative cases were associated with a
DNA methylationpattern of the more aggressive types among the recently introduced
DNA methylationgroups. Also, NF2 and SUFU mutations were enriched among cases with complete lack of H3K27me3 staining in tumor cells (p < 0.0001 and p = 0.029, respectively). H3K27me3 staining pattern added significant prognostic insight into WHO grade II cases and in the compound subset of WHO grade I and II cases (p = 0.04 and p = 0.007, respectively). However, it did not further stratify within WHO grade III cases. Collectively, these data indicate that epigenetic modifications beyond
DNA methylationare involved in the aggressiveness of
meningioma. It also suggests that H3K27me3 immunohistochemistry might be a useful adjunct in
meningiomadiagnostics, particularly for cases with WHO grade II histology or at the borderline between WHO grade I and II.
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