Advances in Research on Human Meningiomas

Meningiomas are the most common intracranial tumours in humans, constituting more than one third [...

The anti-apoptotic protein survivin can improve the prognostication of meningioma patients

Background The 2016 WHO histopathological grading includes a substantial within-variation in recurrence risk, and is thus insufficient to predict prognosis after initial surgery of patients suffering from meningiomas. The aim of this study was to compare the prognostic value of the histopathological grading and the conventional biomarker MIB-1 with expression of the anti-apoptotic protein survivin to see if this biomarker could complement recurrence prediction. Methods Using immunohistochemistry, the expression of MIB-1 and survivin were determined as labeling indices (LIs) in tissue micro arrays from 160 human meningiomas. The accuracy of prognostication was assessed with receiver operator characteristics analyses and standard survival analyses. Results The expression of survivin was significantly associated with both histopathological grade (P = 0.022) and recurrence status (P = 0.035). A survivin LI of 1% was identified as the optimal cutoff value to predict recurrence (P = 0.003), and was proven as more reliable than the histopathological grading (P = 0.497) and MIB-1 expression (P = 0.091). This result was further strengthened in multivariate analyses where survivin expression was revealed as an independent predictor of recurrence-free survival, while the histopathological grading and MIB-1 expression did not reach significance (P ≥ 0.156). Conclusions These findings suggest that incorporation of survivin in the clinical practice might be useful as complement for the histopathological grading and should further be evaluated in independent prospective studies

Evaluation of the proliferation markers Ki-67/MIB-1, mitosin, survivin, pHH3, and DNA topoisomerase II alpha in human anaplastic astrocytomas - an immunohistochemical study

Background Histological malignancy grading of astrocytomas can be challenging despite criteria given by the World Health Organisation (WHO). Grading is fundamental for optimal prognostication and treatment, and additional biomarkers are needed to support the histopathological diagnosis. Estimation of proliferative activity has gained much enthusiasm, and the present study was designed to evaluate and compare novel immunohistochemical proliferative markers in human anaplastic astrocytomas. Methods Proliferative activity was determined in twenty-seven cases with antibodies reactive against the Ki-67 antigen, mitosin, survivin, pHH3, and DNA topoisomerase IIα, and they were mutually compared as well as related to mitotic activity. Results The markers correlated well with each other, but poorly with mitoses, probably because of small and squeezed tumour samples, in which identification of mitoses can be difficult. Positive association to overall survival was observed as well. Conclusions Our data show that these markers may assist significantly in the evaluation of proliferative activity in anaplastic astrocytomas and even have prognostic value

Progressive multifocal leukoencephalopathy in an immunocompetent patient?

Background: Progressive multifocal leukoencephalopathy (PML) is a rapidly progressive, potentially fatal, demyelinating disease affecting immunosuppressed patients. PML is rarely reported in cases with no underlying disease or immunosuppression-associated condition. Case Report: We present a 72-year-old previously healthy woman who developed a progressive neurological condition affecting the entire nervous system which led to her death within 5 months. PML was diagnosed at autopsy. Conclusion: PML should be considered in patients with progressive neurological disorders involving the white matter, even in the absence of previous immunomodulatory treatment or immunosuppression

The histological representativeness of glioblastoma tissue samples

Background Glioblastomas (GBMs) are known for having a vastly heterogenous histopathology. Several studies have shown that GBMs can be histologically undergraded due to sampling errors of small tissue samples. We sought to explore to what extent histological features in GBMs are dependent on the amount of viable tissue on routine slides from both biopsied and resected tumors. Methods In 106 newly diagnosed GBM patients, we investigated associations between the presence or degree of 24 histopathological and two immunohistochemical features and the tissue amount on hematoxylin-eosin (HE) slides. The amount of viable tissue was semiquantitatively categorized as “sparse,” “medium,” or “substantial” for each case. Tissue amount was also assessed for associations with MRI volumetrics and the type of surgical procedure. Results About half (46%) of the assessed histological and immunohistochemical features were significantly associated with tissue amount. The significant features were less present or of a lesser degree when the tissue amount was smaller. Among the significant features were most of the features relevant for diffuse astrocytic tumor grading, i.e., small necroses, palisades, microvascular proliferation, atypia, mitotic count, and Ki-67/MIB-1 proliferative index (PI). Conclusion A substantial proportion of the assessed histological features were at risk of being underrepresented when the amount of viable tissue on HE slides was limited. Most of the grading features were dependent on tissue amount, which underlines the importance of considering sampling errors in diffuse astrocytic tumor grading. Our findings also highlight the importance of adequate tissue collection to increase the quality of diagnostics and histological research

Expression and clinical significance of the proliferation marker minichromosome maintenance protein 2 (Mcm2) in diffuse astrocytomas WHO grade II

Background The WHO classification system for astrocytomas is not considered optimal, mainly because of the subjective assessment of the histopathological features. Few prognostic variables have been found that stratify the risk of clinical progression in patients with grade II astrocytoma. For that reason there is a continuous search for biomarkers that can improve the histopathological diagnosis and prognostication of these tumours. Aim This study was designed to investigate the prognostic significance of the proliferative marker Mcm2 (minichromosome maintenance protein 2) in diffuse astrocytomas WHO grade II and correlate the findings with histopathology, mitoses, and Ki67/MIB-1 immunostaining. Method 61 patients with histologically verified grade II astrocytoma (WHO 2007) were investigated. Paraffin sections were immunostained with anti-Mcm2, and the Mcm2 proliferative index (PI) was determined as the percentage of immunoreactive tumour cell nuclei. Results Mcm2 PI was not associated with any histopathological features but correlated significantly with mitotic count and Ki67/MIB-1 PI (p0.05). Conclusions In our hands Mcm2 immunostaining has no advantage over Ki67/MIB-1 in the evaluation of grade II astrocytomas. Larger studies are needed to fully clarify the prognostic role of this biomarker. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/171500279194403

Prognostic value of ErbB2/HER2 in human meningiomas

Introduction Among clinical challenges regarding human meningiomas is their propensity to recur even in cases with benign histology. Reliable biomarkers that can identify these cases are therefore highly desired. ErbB2/HER2 status is important in the medical management of patients with various human malignancies, whereas its clinical relevance in human meningiomas is ambiguous. For this reason, we wanted to investigate the expression of intra- and extracellular domains of ErbB2/HER2 as well as the level of activated receptor in these tumors. Further, we wanted to elucidate any clinicopathological associations to antibody expression and if gene amplification was present. Methods In total, 186 human meningiomas of all malignancy grades were included in the study, 163 of these were in tissue microarrays (TMA). Antibody expression was assessed by means of immunohistochemistry (IHC) and gene amplification by fluorescence in situ hybridization (FISH). Results All cases were immunoreactive with antibodies targeting the intracellular domain, whereas about 48% and 11% were positive with antibodies against the extracellular domain and against the activated receptor, respectively. Normal meninges were not immunoreactive. There were no relations to malignancy grade, and only the activated receptor was significantly correlated with increased risk for recurrence or death (time to recurrence: HR 1.568, CI (1.153 to 2.132), p = 0.004). No gene amplification was found. Conclusion ErbB2/HER2 is generally upregulated in human meningiomas, but in an activated state only in a few cases. Only the activated receptor is associated with poorer prognosis, a link that needs further investigations.publishedVersion© 2018 Arnli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Are there predilection sites for intracranial meningioma? A population-based atlas

Meningioma is the most common benign intracranial tumor and is believed to arise from arachnoid cap cells of arachnoid granulations. We sought to develop a population-based atlas from pre-treatment MRIs to explore the distribution of intracranial meningiomas and to explore risk factors for development of intracranial meningiomas in different locations. All adults (≥ 18 years old) diagnosed with intracranial meningiomas and referred to the department of neurosurgery from a defined catchment region between 2006 and 2015 were eligible for inclusion. Pre-treatment T1 contrast-enhanced MRI-weighted brain scans were used for semi-automated tumor segmentation to develop the meningioma atlas. Patient variables used in the statistical analyses included age, gender, tumor locations, WHO grade and tumor volume. A total of 602 patients with intracranial meningiomas were identified for the development of the brain tumor atlas from a wide and defined catchment region. The spatial distribution of meningioma within the brain is not uniform, and there were more tumors in the frontal region, especially parasagittally, along the anterior part of the falx, and on the skull base of the frontal and middle cranial fossa. More than 2/3 meningioma patients were females (p < 0.001) who also were more likely to have multiple meningiomas (p < 0.01), while men more often have supratentorial meningiomas (p < 0.01). Tumor location was not associated with age or WHO grade. The distribution of meningioma exhibits an anterior to posterior gradient in the brain. Distribution of meningiomas in the general population is not dependent on histopathological WHO grade, but may be gender-related.publishedVersio