H3K27me3 loss indicates an increased risk of recurrence in the Tübingen meningioma cohort

Abstract

Background A loss of the trimethylation of lysine 27 of histone H3 (H3K27me3) in meningioma has been recently suggested as an adjunct to identify subsets of higher risk of recurrence. The aim of the present study was to assess the prognostic value of H3K27 histone trimethylation and its potential clinical utility in the “Tübingen meningioma cohort”. Methods Patients who underwent meningioma resection between 10/2003 and 1/22015 at the University Hospital Tübingen were included. Immunohistochemical stainings for H3K27me3 and the proliferation marker MIB1 were assessed and correlated with clinical parameters using univariate and multivariate cox regressions as well as Pearson’s chi-squared and log-rank test. Results Overall, 1268 meningiomas were analyzed with a female to male ratio of 2.6 and a mean age of 58.7 years (range 8.3 – 91.0). With 163 cases lost to follow up, 1103 cases were available for further analysis with a mean follow-up of 40.3 months (range 1.1 – 186.3). Male gender, younger age, intracranial tumor localization, progressive tumor, subtotal resection, higher WHO grade, increased MIB1 rate and loss of H3K27me3 were significant negative prognostic factors in the univariate analysis. H3K27me3 status and all other prognostic factors, except age and tumor location, remained significant in the multivariate model. Furthermore, adjuvant radiotherapy was an independent positive prognostic factor. Conclusions Loss of H3K27me3 combined with MIB1 labeling index are independent prognostic factors in meningioma. These data from the Tübingen meningioma cohort support the clinical utility of H3K27me3 immunohistochemical staining in meningioma and its integration into the routine histopathological workup.

Brain Invasion in Meningioma—A Prognostic Potential Worth Exploring

“…On a molecular level, tumors can be roughly dichotomized as NF2 (neurofibromatosis type 2) and non-NF2-mutated meningiomas, and NF2 is the main identified driver mutation in atypical meningiomas [9,10]. Mutations of the promotor of the telomere reverse transcriptase (TERT), loss of the cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) and loss of the trimethylation of lysin 27 of histone 3 (H3K27me3), were identified as negative prognostic markers independent of tumor histology [11][12][13][14].…”

Mib1 Expression Is Increased in Meningiomas with Histopathological Evidence of Cns Invasion

“…We have therefore used a computerized quantification method to control for an interobserver bias and to obtain continual numerical values. We have recently demonstrated the independent significant prognostic impact of quantified MIB1 expression in our meningioma cohort [20].…”

Increased proliferation is associated with CNS invasion in meningiomas

“…We have therefore used a computerized quantification method to control for an interobserver bias and to obtain continual numerical values. We have recently demonstrated the independent significant prognostic impact of quantified Ki67 expression in our meningioma cohort [ 23 ]. However, it must be kept in mind, that Ki67 positivity may also include proliferating inflammatory cells and therefore may suggest falsely increased proliferation characteristics.…”