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Published on: January 9, 2019
Loss of H3K27me3 in WHO grade 3 meningioma
Andrea Daniela Maier1,2, Christian Beltoft Brøchner3, Christian Mirian4
1Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 6, Copenhagen, Denmark. andrea.maier@regionh.dk.
Abstract:
Immunohistochemical quantification of H3K27me3 was reported to distinguish meningioma patients with an unfavorable prognosis but is not yet established as a prognostic biomarker within WHO grade 3 meningiomas. We studied H3K27me3 loss in a series of biopsies from primary and secondary malignant meningioma to validate its prognostic performance and describe if loss of H3K27me3 occurs during malignant transformation. Two observers quantified H3K27me3 status as "complete loss", < 50% and > 50% stained cells in 110 tumor samples from a population-based consecutive cohort of 40 WHO grade 3 meningioma patients. We found no difference in overall survival (OS) in patients with > 50% H3K27me3 retention compared to < 50% in the cohort of patients with WHO grade 3 meningioma (Wald test p = 0.5). H3K27me3 staining showed heterogeneity in full section tumor slides while staining of the Barr body and peri-necrotic cells complicated quantification further. H3K27me3 expression differed without a discernible pattern between biopsies from repeated surgeries of meningioma recurrences. In conclusion, our results were not compatible with a systematic pattern of immunohistochemical H3K27me3 loss being associated with OS or malignant transformation of meningiomas and did not support H3K27me3 loss as a useful immunohistochemical biomarker within grade 3 meningiomas due to staining-specific challenges in quantification.
Insights
Loss of H3K27me3 expression does not predict overall survival in WHO grade 3 meningioma patients. Quantification challenges limit its use as a prognostic biomarker in these tumors.
Area of Science:
- Neuro-oncology
- Histopathology
- Cancer Biomarkers
Background:
- H3K27me3 immunohistochemistry shows potential for distinguishing meningioma patients with poor prognosis.
- Its utility as a prognostic biomarker specifically within WHO grade 3 meningiomas remains unestablished.
Purpose of the Study:
- To validate the prognostic performance of H3K27me3 loss in WHO grade 3 meningiomas.
- To investigate if H3K27me3 loss correlates with malignant transformation in meningiomas.
Main Methods:
- Quantification of H3K27me3 status (complete loss, <50%, >50% stained cells) by two observers.
- Analysis of 110 tumor samples from 40 patients with WHO grade 3 meningioma in a population-based cohort.
- Assessment of H3K27me3 expression in primary and recurrent meningioma biopsies.
Main Results:
- No significant difference in overall survival (OS) was observed between patients with >50% H3K27me3 retention and those with <50%.
- H3K27me3 staining exhibited heterogeneity, and quantification was complicated by Barr body and peri-necrotic cell staining.
- No discernible pattern of H3K27me3 expression differences was noted between biopsies from repeated surgeries for meningioma recurrences.
Conclusions:
- H3K27me3 loss does not appear to be systematically associated with OS or malignant transformation in meningiomas.
- Staining-specific quantification challenges preclude H3K27me3 loss from being a reliable immunohistochemical biomarker in WHO grade 3 meningiomas.
