Skip to main content

Advertisement

SpringerLink
Log in

The status of MGMT protein expression is a prognostic factor for meningeal hemangiopericytoma: a clinicopathologic and immunohistochemical study of 12 cases at a single institution

  • CLINICAL STUDY – PATIENT STUDY
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Meningeal hemangiopericytoma (HPC) is a clinicopathologically well-characterized malignancy with a high tendency to recur locally and to metastasize outside the central nervous system (CNS). We render clinicopathologic features of 12 cases of this uncommon tumor to further elucidate the relationship between the status of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) and the prognosis. Twenty-five specimens of meningeal HPC belonging to 12 patients were obtained at a single institution from 1992 to 2001. Correlations of histologic parameters, immunohistochemical study and clinical features were assessed. This series included five men and seven women with a median age of 37.5 years at the first surgery. The median post-operative follow-up period was 7.6 years. Six patients (55%) had single or multiple local tumor recurrences. The mean time to recurrence was 6.7 years. Distant metastasis occurred in three patients (27%) at a mean time of 6.5 years after first operation. The most frequent metastatic sites were liver and lung. Histopathologically, eight primary tumors (67%) belonged to WHO grade II, while four primary tumors (33%) belonged to WHO grade III. Immunohistochemically, 18% primary tumors exhibited 3+ to 4+ nuclear staining for MGMT protein, 18% exhibited 2+ staining, and 64% exhibited 0 to 1+ staining. The overall survival rate was 67 and 33% for primary tumors with 0 to 1+ and 2+ to 4+ MGMT staining, respectively (P = 0.018). The study illustrates aggressive behavior of meningeal HPC and the prognostic value of the status of MGMT protein expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Stout AP, Murray MR (1942) Hemangiopericytoma: a vascular tumor featuring Zimmermann’s pericytes. Ann Surg 116:26–33

    Article  PubMed  CAS  Google Scholar 

  2. Dardick I, Hammar SP, Scheithauer BW (1989) Ultrastructural spectrum of hemangiopericytoma: a comparative study of fetal, adult, and neoplastic pericytes. Ultrastruct Pathol 13:111–154

    Article  PubMed  CAS  Google Scholar 

  3. Battifora H (1973) Hemangiopericytoma: ultrastructural study of five cases. Cancer 31:1418–1432

    Article  PubMed  CAS  Google Scholar 

  4. D’Amore ES, Manivel JC, Sung JH (1990) Soft-tissue and meningeal hemangiopericytomas: an immunohistochemical and ultrastructural study. Hum Pathol 21:414–423

    Article  PubMed  Google Scholar 

  5. Porter PL, Bigler SA, McNutt M, Gown AM (1991) The immunophenotype of hemangiopericytomas and glomus tumors, with special reference to muscle protein expression: an immunohistochemical study and review of the literature. Mod Pathol 4:46–52

    PubMed  CAS  Google Scholar 

  6. Schurch W, Skalli O, Lagace R, Seemayer TA, Gabbiani G (1990) Intermediate filament proteins and actin isoforms as markers for soft-tissue tumor differentiation and origin. III. Hemangiopericytomas and glomus tumors. Am J Pathol 136:771–786

    PubMed  CAS  Google Scholar 

  7. Nemes Z (1992) Differentiation markers in hemangiopericytoma. Cancer 69:133–140

    Article  PubMed  CAS  Google Scholar 

  8. Middleton LP, Duray PH, Merino MJ (1998) The histological spectrum of hemangiopericytoma: application of immunohistochemical analysis including proliferative markers to facilitate diagnosis and predict prognosis. Hum Pathol 29:636–640

    Article  PubMed  CAS  Google Scholar 

  9. el-Naggar AK, Ro JY, Ayala AG, Ward R, Ordonez NG (1989) Localized fibrous tumor of the serosal cavities. Immunohistochemical, electron-microscopic, and flow-cytometric DNA study. Am J Clin Pathol 92:561–565

    PubMed  CAS  Google Scholar 

  10. Moran CA, Suster S, Koss MN (1992) The spectrum of histologic growth patterns in benign and malignant fibrous tumors of the pleura. Semin Diagn Pathol 9:169–180

    PubMed  CAS  Google Scholar 

  11. van de Rijn M, Lombard CM, Rouse RV (1994) Expression of CD34 by solitary fibrous tumors of the pleura, mediastinum, and lung. Am J Surg Pathol 18:814–820

    Article  PubMed  Google Scholar 

  12. Hanau CA, Miettinen M (1995) Solitary fibrous tumor: histological and immunohistochemical spectrum of benign and malignant variants presenting at different sites. Hum Pathol 26:440–449

    Article  PubMed  CAS  Google Scholar 

  13. Guillou L, Fletcher JA, Fletcher CDM, Mandahl N (2002) Extrapleural solitary fibrous tumour and haemangiopericytoma. In: Fletcher CD, Unni KK, Mertens F (eds) World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone, 3rd edn. IARC Press, Lyon, pp 86–90

    Google Scholar 

  14. Weiss SW, Goldblum JR (2008) Enzinger and Weiss’s soft tissue tumors, 5th edn. Mosby, St. Louis, pp 1120–1134

    Google Scholar 

  15. Bailey P, Cushing H, Eisenhardt L (1928) Angioblastic meningioma. Arch Pathol 6:953–990

    Google Scholar 

  16. Giannini C, Rushing EJ, Hainfellner JA (2007) Haemangiopericytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system. IARC Press, Lyon, pp 178–180

    Google Scholar 

  17. Tihan T, Viglione M, Rosenblum MK, Olivi A, Burger PC (2003) Solitary fibrous tumors in the central nervous system. A clinicopathologic review of 18 cases and comparison to meningeal hemangiopericytomas. Arch Pathol Lab Med 127:432–439

    PubMed  Google Scholar 

  18. Mena H, Ribas JL, Pezeshkpour GH, Cowan DN, Parisi JE (1991) Hemangiopericytoma of the central nervous system: a review of 94 cases. Hum Pathol 22:84–91

    Article  PubMed  CAS  Google Scholar 

  19. Soyuer S, Chang EL, Selek U, McCutcheon IE, Maor MH (2004) Intracranial meningeal hemangiopericytoma: the role of radiotherapy: report of 29 cases and review of the literature. Cancer 100:1491–1497

    Article  PubMed  Google Scholar 

  20. Kim JH, Jung HW, Kim YS, Kim CJ, Hwang SK, Paek SH, Kim DG, Kwun BD (2003) Meningeal hemangiopericytomas: long-term outcome and biological behavior. Surg Neurol 59:47–53

    Article  PubMed  Google Scholar 

  21. Guthrie BL, Ebersold MJ, Scheithauer BW, Shaw EG (1989) Meningeal hemangiopericytoma: histopathological features, treatment, and long-term follow-up of 44 cases. Neurosurgery 25:514–522

    Article  PubMed  CAS  Google Scholar 

  22. Galanis E, Buckner JC, Scheithauer BW, Kimmel DW, Schomberg PJ, Piepgras DG (1998) Management of recurrent meningeal hemangiopericytoma. Cancer 82:1915–1920

    Article  PubMed  CAS  Google Scholar 

  23. Ludlum DB (1990) DNA alkylation by the haloethylnitrosoureas: nature of modifications produced and their enzymatic repair or removal. Mutat Res 233:117–126

    Article  PubMed  CAS  Google Scholar 

  24. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003

    Article  PubMed  CAS  Google Scholar 

  25. Uhm JH, Ballman KV, Wu W, Giannini C, Krauss JC, Buckner JC, James CD, Scheithauer BW, Behrens RJ, Flynn PJ, Schaefer PL, Dakhill SR, Jaeckle KA (2010) Phase II evaluation of Gefitinib in patients with newly diagnosed grade 4 astrocytoma: Mayo/North Central Cancer Treatment Group study N0074. Int J Radiat Oncol Biol Phys 80:347–353

    Article  PubMed  Google Scholar 

  26. Raizer JJ, Abrey LE, Lassman AB, Chang SM, Lamborn KR, Kuhn JG, Yung WK, Gilbert MR, Aldape KA, Wen PY, Fine HA, Mehta M, Deangelis LM, Lieberman F, Cloughesy TF, Robins HI, Dancey J, Prados MD (2010) A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy. Neuro Oncol 12:95–103

    PubMed  CAS  Google Scholar 

  27. Simpson D (1957) The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:22–39

    Article  PubMed  CAS  Google Scholar 

  28. Burger PC, Scheithauer BW (2007) Tumors of the central nervous system. AFIP atlas of tumor pathology, 4th ser, fasc 7. American Registry of Pathology; Armed Forces Institute of Pathology, Washington, DC, pp 373–378

    Google Scholar 

  29. Perry A, Scheithauer BW, Nascimento AG (1997) The immunophenotypic spectrum of meningeal hemangiopericytoma: a comparison with fibrous meningioma and solitary fibrous tumor of meninges. Am J Surg Pathol 21:1354–1360

    Article  PubMed  CAS  Google Scholar 

  30. Goellner JR, Laws ER Jr, Soule EH, Okazaki H (1978) Hemangiopericytoma of the meninges. Mayo clinic experience. Am J Clin Pathol 70:375–380

    PubMed  CAS  Google Scholar 

  31. Jaaskelainen J, Servo A, Haltia M, Wahlstrom T, Valtonen S (1985) Intracranial hemangiopericytoma: radiology, surgery, radiotherapy, and outcome in 21 patients. Surg Neurol 23:227–236

    Article  PubMed  CAS  Google Scholar 

  32. Ecker RD, Marsh WR, Pollock BE, Kurtkaya-Yapicier O, McClelland R, Scheithauer BW, Buckner JC (2003) Hemangiopericytoma in the central nervous system: treatment, pathological features, and long-term follow up in 38 patients. J Neurosurg 98:1182–1187

    Article  PubMed  Google Scholar 

  33. Dufour H, Metellus P, Fuentes S, Murracciole X, Regis J, Figarella-Branger D, Grisoli F (2001) Meningeal hemangiopericytoma: a retrospective study of 21 patients with special review of postoperative external radiotherapy. Neurosurgery 48:756–762

    PubMed  CAS  Google Scholar 

  34. Coffey RJ, Cascino TL, Shaw EG (1993) Radiosurgical treatment of recurrent hemangiopericytomas of the meninges: preliminary results. J Neurosurg 78:903–908

    Article  PubMed  CAS  Google Scholar 

  35. Sheehan J, Kondziolka D, Flickinger J, Lunsford LD (2002) Radiosurgery for treatment of recurrent intracranial hemangiopericytomas. Neurosurgery 51:905–910

    PubMed  Google Scholar 

  36. Chamberlain MC, Glantz MJ (2008) Sequential salvage chemotherapy for recurrent intracranial hemangiopericytoma. Neurosurgery 63:720–726

    Article  PubMed  Google Scholar 

  37. Qian XC, Brent TP (1997) Methylation hot spots in the 5′ flanking region denote silencing of the O6-methylguanine-DNA methyltransferase gene. Cancer Res 57:3672–3677

    PubMed  CAS  Google Scholar 

  38. Watts GS, Pieper RO, Costello JF, Peng YM, Dalton WS, Futscher BW (1997) Methylation of discrete regions of the O6-methylguanine DNA methyltransferase (MGMT) CpG island is associated with heterochromatinization of the MGMT transcription start site and silencing of the gene. Mol Cell Biol 17:5612–5619

    PubMed  CAS  Google Scholar 

  39. Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59:793–797

    PubMed  CAS  Google Scholar 

  40. Pegg AE, Dolan ME, Moschel RC (1995) Structure, function, and inhibition of O6-alkylguanine-DNA alkyltransferase. Prog Nucl Acid Res Mol Biol 51:167–223

    Article  CAS  Google Scholar 

  41. Jaeckle KA, Eyre HJ, Townsend JJ, Schulman S, Knudson HM, Belanich M, Yarosh DB, Bearman SI, Giroux DJ, Schold SC (1998) Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J Clin Oncol 16:3310–3315

    PubMed  CAS  Google Scholar 

  42. Silber JR, Blank A, Bobola MS, Ghatan S, Kolstoe DD, Berger MS (1999) O6-methylguanine-DNA methyltransferase-deficient phenotype in human gliomas: frequency and time to tumor progression after alkylating agent-based chemotherapy. Clin Cancer Res 5:807–814

    PubMed  CAS  Google Scholar 

  43. Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354

    Article  PubMed  CAS  Google Scholar 

  44. Fuller GN, Bigner SH (1992) Amplified cellular oncogenes in neoplasms of the human central nervous system. Mutat Res 276:299–306

    PubMed  CAS  Google Scholar 

  45. Wikstrand CJ, Reist CJ, Archer GE, Zalutsky MR, Bigner DD (1998) The class III variant of the epidermal growth factor receptor (EGFRvIII): characterization and utilization as an immunotherapeutic target. J Neurovirol 4:148–158

    Article  PubMed  CAS  Google Scholar 

  46. Wernicke AG, Dicker AP, Whiton M, Ivanidze J, Hyslop T, Hammond EH, Perry A, Andrews DW, Kenyon L (2010) Assessment of epidermal growth factor receptor (EGFR) expression in human meningioma. Radiat Oncol 5:46

    Article  PubMed  Google Scholar 

  47. Park MS, Patel SR, Ludwig JA, Trent JC, Conrad CA, Lazar AJ, Choi H, Benjamin RS, Araujo DM (2008) Combination therapy with temozolomide and bevacizumab in the treatment of hemangiopericytoma/malignant solitary fibrous tumor. J Clin Oncol 26 suppl:10512 (abstract)

  48. Kim JT, Kim JS, Ko KW, Kong DS, Kang CM, Kim MH, Son MJ, Song HS, Shin HJ, Lee DS, Eoh W, Nam DH (2006) Metronomic treatment of temozolomide inhibits tumor cell growth through reduction of angiogenesis and augmentation of apoptosis in orthotopic models of gliomas. Oncol Rep 16:33–39

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta-Pei Road, Niao Sung, Kaohsiung, 83301, Taiwan

    I-Wei Chang, Jui-Wei Lin & You-Ting Wu

Authors
  1. I-Wei Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jui-Wei Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. You-Ting Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to You-Ting Wu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, IW., Lin, JW. & Wu, YT. The status of MGMT protein expression is a prognostic factor for meningeal hemangiopericytoma: a clinicopathologic and immunohistochemical study of 12 cases at a single institution. J Neurooncol 105, 563–572 (2011). https://doi.org/10.1007/s11060-011-0620-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-011-0620-7

Keywords

Search

Navigation