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.
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology NTNU, Norway.
Thomas
T
Backer-Grøndahl
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology NTNU, Norway.
Bjørnar H
BH
Moen
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology NTNU, Norway.
Magnus B
MB
Arnli
Department of Pathology and Medical Genetics, St. Olavs Hospital, Trondheim University Hospital Norway.
Kathrin
K
Torseth
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology NTNU, Norway ; Department of Pathology and Medical Genetics, St. Olavs Hospital, Trondheim University Hospital Norway.
Sverre H
SH
Torp
D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002448:Cell Adhesion; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008577:Meningeal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008579:Meningioma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
CD4; E-cadherin; EMA; GFAP; Ki-67/MIB-1; MMP-9; PAI-1; PHH3; cathepsin D; collagen IV