The Immunohistochemical Loss of H3K27me3 in Intracranial Meningiomas Predicts Shorter Progression-Free Survival after Stereotactic Radiosurgery

Abstract

The immunohistochemical loss of histone H3 trimethylated in lysine 27 (H3K27me3) was recently shown to predict recurrence of meningiomas after surgery. However, its association with tumor progression after stereotactic radiosurgery (SRS) is unexplored. To investigate whether H3K27 methylation status may predict progression-free survival (PFS) after SRS, we assessed H3K27me3 immunoexpression in thirty-nine treatment naïve, intracranial, meningiomas, treated with surgery and subsequent SRS for residual (twenty-three cases) or recurrent (sixteen cases) disease. H3K27me3 immunostaining was lost in seven meningiomas, retained in twenty-seven and inconclusive in five. Six of the seven meningiomas (86%) with H3K27me3 loss had tumor progression after SRS, compared to nine of twenty-seven (33%) with H3K27me3 retention (p = 0.0143). In addition, patients harboring a meningioma with H3K27me3 loss had significantly shorter PFS after SRS (range: 10–81 months; median: 34 months), compared to patients featuring a meningioma with retained H3K27me3 (range: 9–143 months; median: 62 months) (p = 0.0036). Nonetheless, tumor sagittal location was the only significant prognostic variable at multivariate analysis for PFS after SRS (p = 0.0142). These findings suggest a previously unreported role of H3K27me3 as a predictor of meningioma progression after SRS for recurrent or residual disease. Modulation of H3K27 methylation status may represent a novel therapeutic strategy to induce radiosensitization of meningiomas.