Journal of Neuro-Oncology

, Volume 73, Issue 3, pp 219–223 | Cite as

High throughput screening of meningioma biomarkers using a tissue microarray

  • Eriks A. Lusis
  • Michael R. Chicoine
  • Arie Perry
Laboratory Investigation


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.


biomarkers 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


progesterone receptor


tissue microarray


vascular endothelial growth factor


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    CBTRUS: Statistical Report (2002) Primary Brain Tumors in the United States. Published by the Central Brain Tumor Registry of the United StatesGoogle Scholar
  2. 2.
    Perry, A, Scheithauer, BW, Stafford, SL, Lohse, CM, Wollan, PC 1999“Malignancy” in meningiomas: a clinicopathologic study of 116 patientsCancer8520462056PubMedGoogle Scholar
  3. 3.
    Louis, DN, Scheithauer, BW, Budka, H, Deimling, A, Kepes, JJ 2000MeningiomasKleihues, PCavenee, W eds. World Health Organization Classification of Tumours Pathology and Genetics of Tumours of the Nervous SystemIARC pressLyon176189Google Scholar
  4. 4.
    Kononen, J, Bubendorf, L, Kallioniemi, A, Barlund, M, Schraml, P, Leighton, S, Torhorst, J, Mihatsch, MJ, Sauter, G, Kallioniemi, OP 1998Tissue microarrays for high-throughput molecular profiling of tumor specimensNat Med4844847CrossRefPubMedGoogle Scholar
  5. 5.
    Chung, GG, Provost, E, Kielhorn, EP, Charette, LA, Smith, BL, Rimm, DL 2001Tissue microarray analysis of beta-catenin in colorectal cancer shows nuclear phospho-beta-catenin is associated with a better prognosisClin Cancer Res740134020PubMedGoogle Scholar
  6. 6.
    Jourdan, F, Sebbagh, N, Comperat, E, Mourra, N, Flahault, A, Olschwang, S, Duval, A, Hamelin, R, Flejou, JF 2003Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expressionVirchows Arch443115121CrossRefPubMedGoogle Scholar
  7. 7.
    Das, A, Tan, WL, Smith, DR 2003Expression of the inhibitor of apoptosis protein survivin in benign meningiomasCancer Lett193217223CrossRefPubMedGoogle Scholar
  8. 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
  9. 9.
    Howng, SL, Wu, CH, Cheng, TS, Sy, WD, Lin, PC, Wang, C, Hong, YR 2002Differential expression of Wnt genes, beta-catenin and E-cadherin in human brain tumorsCancer Lett18395101CrossRefPubMedGoogle Scholar
  10. 10.
    Jones, NR, Rossi, ML, Gregoriou, M, Hughes, JT 1990Epidermal growth factor receptor expression in 72 meningiomasCancer66152155PubMedGoogle Scholar
  11. 11.
    Katoh, M, Wilmotte, R, Belkouch, MC, Tribolet, N, Pizzolato, G, Dietrich, PY 2003Survivin in brain tumors: an attractive target for immunotherapyJ Neurooncol647176CrossRefPubMedGoogle Scholar
  12. 12.
    Nishikawa, R, Cheng, SY, Nagashima, R, Huang, HJ, Cavenee, WK, Matsutani, M 1998Expression of vascular endothelial growth factor in human brain tumorsActa Neuropathol (Berl)96453462CrossRefGoogle Scholar
  13. 13.
    Yang, SY, Xu, GM 2001Expression of PDGF and its receptor as well as their relationship to proliferating activity and apoptosis of meningiomas in human meningiomasJ Clin Neurosci (Suppl 1)84953CrossRefGoogle Scholar
  14. 14.
    Zhang, Z, Zhao, H, Zhu, X 2000Vascular endothelial factor of meningiomas and peritumoural vasogenic brain edemaZhonghua Wai Ke Za Zhi382830PubMedGoogle Scholar
  15. 15.
    Castilla, EA, Prayson, RA, Abramovich, CM, Cohen, ML 2003Immunohistochemical expression of cathepsin D in meningiomasAm J Clin Pathol119123128CrossRefPubMedGoogle Scholar
  16. 16.
    Nappi, O, Ritter, JH, Pettinato, G, Wick, MR 1995Hemangiopericytoma: histopathological pattern or clinicopathologic entity?Semin Diagn Pathol12221232PubMedGoogle Scholar
  17. 17.
    Bouvier-Labit, C, Liprandi, A, Piercecchi, MD, Hosseini, H, Henin, D, Figarella-Branger, D 2000Contribution of immunohistochemistry and electron microscopy for the diagnosis of meningeal hemangiopericytomas. 15 case reportsAnn Pathol20492498PubMedGoogle Scholar
  18. 18.
    Perry, A, Scheithauer, BW, Nascimento, AG 1997The immunophenotypic spectrum of meningeal hemangiopericytoma: a comparison with fibrous meningioma and solitary fibrous tumor of meningesAm J Surg Pathol2113541360CrossRefPubMedGoogle Scholar
  19. 19.
    Rajaram, V, Brat, DJ, Perry, A 2004Anaplastic meningioma vs. meningeal hemangiopericytoma: immunohistochemical and genetic markersHum Pathol3514131418CrossRefPubMedGoogle Scholar
  20. 20.
    Artlich, A, Schmidt, D 1990Immunohistochemical profile of meningiomas and their histological subtypesHum Pathol21843849CrossRefPubMedGoogle Scholar
  21. 21.
    Schnitt, SJ, Vogel, H 1986Meningiomas: diagnostic value of immunoperoxidase staining for epithelial membrane antigenAm J Surg Pathol10640649PubMedGoogle Scholar
  22. 22.
    Hsu, DW, Efird, JT, Hedley-Whyte, ET 1997Progesterone and estrogen receptors in meningiomas: prognostic considerationsJ Neurosurg86113120Google Scholar
  23. 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

Copyright information

© Springer 2005

Authors and Affiliations

  • Eriks A. Lusis
    • 1
  • Michael R. Chicoine
    • 2
  • Arie Perry
    • 1
  1. 1.Division of NeuropathologyWashington University School of MedicineSt. LouisUSA
  2. 2.Division of NeurosurgeryWashington University School of MedicineSt. LouisUSA

Personalised recommendations