Immunohistochemical characterization of brain-invasive meningiomas.

Brain-invasive meningiomas have an adverse prognosis, so it is important to detect and correctly evaluate brain invasion by light microscopy. Furthermore, the underlying biological mechanisms responsible for brain-invasive growth are incompletely understood. The primary aim of this study was to identify immunohistochemical markers that could improve identification and evaluation of brain invasion in meningiomas. A second aim was to investigate the process of brain invasion using immunohistochemical markers of proliferation, extracellular matrix modulation, and cell adhesion. From a series of 196 human meningiomas, 67 cases were selected for analysis because of the presence of brain tissue in tumor specimens. Fourteen of these 67 meningiomas were brain-invasive. Invasiveness was determined primarily by evaluation of hematoxylin-erytrosin-saffron- (HES-) stained specimens, although glial fibrillary acidic protein (GFAP), anti-collagen IV, and cluster of differentiation 44 (CD44) markers provided additional information. It was important to examine microscopic sections from various levels of the paraffin-embedded tissue block to adequately assess invasiveness. Sections stained using antibodies against Ki-67/MIB-1, phospohistone-H3 (PHH3), matrix metalloproteinase-9 (MMP-9), cathepsin D, plasminogen activator inhibitor-1 (PAI-1), and E-cadherin antigens were used to characterize brain-invasive meningiomas and to investigate the process of brain invasion. Only increased expression of the extracellular matrix modulator MMP-9 correlated with brain-invasive growth (p=0.025). Examination of HES-stained sections identified brain invasion. Use of relevant immunohistochemical markers did not contribute substantially to this evaluation. Evaluation of stepwise sections should be considered when brain-invasive growth is suspected. MMP-9 may be an important mediator of brain-invasive growth.

Histopathology and prognosis in human meningiomas.

Histopathological grading of human meningiomas is based on criteria adopted by the World Health Organization (WHO). However, interpretation of the defined histopathological criteria is often subjective. The aim of this study was to investigate the clinical and histopathological features in these tumours associated with patient survival. This enables evaluation of current grading guidelines and practice. In this study, 196 primary, intracranial, and consecutively treated patients from one institution were included. All histological sections were reviewed. Survival data were controlled with the Norwegian Cause of Death Registry. Falcine location, sheet-like growth, frequent mitoses, subtotal resection grade, and absence of psammoma bodies were strong prognostic factors. Of these factors, the latter two were statistically significantly associated with decreased time to recurrence in multivariate analyses. The WHO 2000 and 2007 classifications were associated with decreased time to recurrence. However, the grading criteria suggested by Ho et al. (2002) and in this study achieved stronger prognostic values. Easily recognizable histopathological criteria are essential in tumour grading. We suggest that any two of the following three variables can be used to recognize atypical (grade II) meningiomas: absence of psammoma bodies, presence of necrosis, and/or ≥4 mitoses per 10 high power fields.

The histopathological spectrum of human meningiomas.

Histopathological examination and grading of meningiomas gives valuable prognostic information, although the method is subject for interobserver variability. The aim of this study was to review a large series of human meningiomas in order to examine the frequency of benign (grade I), atypical (grade II), and anaplastic (grade III) forms depending on various WHO classification schemes. In addition, we wanted to describe the frequency of various histopathological features and their mutual correlations. Sections from 196 consecutively treated primary human meningioma patients were revised retrospectively. The established criteria to grade meningiomas, which are also known to be associated with tumorigenesis, were shown to correlate significantly. The number of grade II meningiomas increased when using the WHO 2007 classification (30%) compared with previous editions, mainly due to the definition of brain infiltrating meningiomas as atypical (grade II). bimodal frequency distribution among age groups of females was observed. Continuous revision of histopathological classification systems is required to improve the diagnostic accuracy.