High throughput screening of meningioma biomarkers using a tissue microarray
Meningiomas are histologically and clinically diverse CNS neoplasms with few available immunohistochemical markers of differentiation and progression. Therefore, we investigated a panel of potentially useful meningioma-associated biomarkers using high throughput tissue microarray immunohistochemistry (TMA-IHC) with a TMA that includes 9 hemangiopericytomas (HPCs) and 41 meningiomas spanning all grades, as well as two subsets of atypical meningiomas, stratified according to clinical behavior. Antibodies utilized were progesterone receptor (PR), epithelial membrane antigen (EMA), cathepsin D, E-cadherin, platelet derived growth factor (PDGF) receptor β, PDGF BB ligand, survivin, epithelial growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). In most cases, frequencies of tumor positivity were similar to those previously reported using whole section IHC. EMA, E-cadherin, and PDGFR-β staining patterns distinguished the anaplastic meningiomas from the HPCs (P < 0.001, P = 0.02, P = 0.015, respectively). As in prior studies, PR and cathepsin D expression were inversely proportional to tumor grade. However, PR and EGFR were also differentially expressed between symptomatic, surgically resected benign meningiomas and incidental meningiomas found at autopsy. We conclude that (1) TMA-IHC is an accurate and efficient way to rapidly assess biomarkers in meningeal tumors, (2) EMA, E-cadherin, and PDGFR-β are useful in distinguishing anaplastic meningiomas from HPCs, and (3) the expression patterns for incidental meningiomas differ slightly from their surgically resected symptomatic counterparts.
Keywordsbiomarkers differentiation hemangiopericytoma immunohistochemistry malignancy meningioma progression tissue microarray
central nervous system
epithelial growth factor receptor
epithelial membrane antigen
platelet derived growth factor
platelet derived growth factor receptor
vascular endothelial growth factor
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- 1.CBTRUS: Statistical Report (2002) Primary Brain Tumors in the United States. Published by the Central Brain Tumor Registry of the United StatesGoogle Scholar
- 3.Louis, DN, Scheithauer, BW, Budka, H, Deimling, A, Kepes, JJ 2000
MeningiomasKleihues, PCavenee, W eds. World Health Organization Classification of Tumours Pathology and Genetics of Tumours of the Nervous SystemIARC pressLyon176189Google Scholar
- 8.Figarella-Branger, D, Vagner-Capodano, AM, Bouillot, P, Graziani, N, Gambarelli, D, Devictor, B, Zattara-Cannoni, H, Bianco, N, Grisoli, F, Pellissier, JF 1994Platelet-derived growth factor (PDGF) and receptor (PDGFR) expression in human meningiomas: correlations with clinicopathological features and cytogenetic analysisNeuropathol Appl Neurobiol20439447PubMedGoogle Scholar
- 22.Hsu, DW, Efird, JT, Hedley-Whyte, ET 1997Progesterone and estrogen receptors in meningiomas: prognostic considerationsJ Neurosurg86113120Google Scholar
- 23.Perry, A, Cai, DX, Scheithauer, BW, Swanson, PE, Lohse, CM, Newsham, IF, Weaver, A, Gutmann, DH 2000Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 casesJ Neuropathol Exp Neurol59872879PubMedGoogle Scholar