Skip to main content
SpringerLink
Log in

Histopathologic predictors of pilocytic astrocytoma event-free survival

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. Most arise in the cerebellum, but they also can develop in the brainstem and optic nerve, where gross total resection (GTR) is not possible. In the absence of GTR, significant variability in both clinical behavior and histology exists. To identify potential markers associated with poor clinical outcome, we retrospectively assessed pathological features in 107 patients with PAs. We identified four pathological features (necrosis, oligodendroglioma-like features, vascular hyalinization, and calcification) that showed a significant correlation with decreased event-free survival (EFS). Similar to previous reports, we also found that PAs involving the optic pathway were associated with worse EFS compared with those arising in other locations. In contrast, mitotic index, p53 immunoreactivity and hyperactivation of several mitogenic signaling pathways (MAPK, CREB, mTOR) did not demonstrate a statistically significant relationship with EFS. Lastly, we did find a statistical trend between EFS and the number of CD68+ cells, suggesting that non-neoplastic elements of the tumor microenvironment may influence subsequent growth and clinical recurrence. Collectively, the identification of specific histopathologic features associated with clinical outcome may improve our ability to determine which PAs are more likely to exhibit clinical progression and require more vigilant observation.

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
Fig. 4

Similar content being viewed by others

References

  1. Bowers DC, Gargan L, Kapur P et al (2003) Study of MIB-1 labelling index as a predictor of tumor progression in pilocytic astrocytomas in children and adolescents. J Clin Oncol 21:2968–2973. doi:10.1200/JCO.2003.01.017

    Article  PubMed  Google Scholar 

  2. CBTRUS (2008) Statistical report: primary brain tumors in the United States, 2000-2004. In: central brain tumor registry of the United States. Available via http://www.cbtrus.org/2005-2006/2005-2006.html. Accessed 9/2008

  3. Cheng Y, Pang JC-S, Ng H-K et al (2003) Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas. Histopathology 37:437–444. doi:10.1046/j.1365-2559.2000.01005.x

    Article  Google Scholar 

  4. Daginakatte GC, Gutmann DH (2007) Neurofibromatosis (NF1) heterozygous brain microglia elaborate paracrine factors that promote NF1-deficient astrocyte and glioma growth. Hum Mol Genet 16:1098–1112. doi:10.1093/hmg/ddm059

    Article  PubMed  CAS  Google Scholar 

  5. Daginakatte GC, Giamino SM, Zhao NW, Parsadanian AS, Gutmann DH (2008) Increased c-Jun-NH2-kinase signaling in neurofibromatosis-1 heterozygous microglia drives microglia activation and promotes optic glioma proliferation. Cancer Res 68:10358–10366

    Article  PubMed  CAS  Google Scholar 

  6. Facoetti A, Ranza E, Nano R (2008) Proliferation and programmed cell death: role of p53 protein in high and low grade astrocytoma. Anticancer Res 28:15–19

    PubMed  CAS  Google Scholar 

  7. Fernandez C, Figarella-Branger D, Girard N et al (2003) Pilocytic astrocytomas in children: prognostic factors—a retrospective study of 80 cases. Neurosurgery 53:544–555. doi:10.1227/01.NEU.0000079330.01541.6E

    Article  PubMed  Google Scholar 

  8. Fisher BJ, Naumova E, Leighton CC et al (2002) Ki-67: a prognostic factor for low-grade glioma? Int J Radiat Oncol Biol Phys 52:996–1001. doi:10.1016/S0360-3016(01)02720-1

    PubMed  Google Scholar 

  9. Gajjar A, Sanford R, Heideman R et al (1997) Low-grade astrocytoma: a decade of experience at St. Jude Children’s Research Hospital. J Clin Oncol 15:2792–2799

    PubMed  CAS  Google Scholar 

  10. Garcia DM, Latifi HR, Simpson JR, Picker S (1989) Astrocytomas of the cerebellum in children. J Neurosurg 71:661–664

    Article  PubMed  CAS  Google Scholar 

  11. Hirsch JF, Sainte Rose C, Pierre-Kahn A, Pfister A, Hoppe-Hirsch E (1989) Benign astrocytic and oligodendrocytic tumors of the cerebral hemispheres in children. J Neurosurg 70:568–572

    Article  PubMed  CAS  Google Scholar 

  12. Hoffman HJ, Soloniuk DS, Humphreys RP et al (1993) Management and outcome of low-grade astrocytomas of the midline in children: a retrospective review. Neurosurgery 33:964–997. doi:10.1097/00006123-199312000-00002

    Article  PubMed  CAS  Google Scholar 

  13. Ishii N, Sawamura Y, Tada M et al (1998) Absence of p53 gene mutations in a tumor panel representative of pilocytic astrocytoma diversity using a p53 functional assay. Int J Cancer 76(6):797–800. doi:10.1002/(SICI)1097-0215(19980610)76:6<797::AID-IJC5>3.0.CO;2-T

    Article  PubMed  CAS  Google Scholar 

  14. Kestle J, Townsend J, Brockmeyer DL, Walker ML (2004) Juvenile pilocytic astrocytoma of the brainstem in children. J Neurosurg (Pediatrics 1) 101:1–6

    Google Scholar 

  15. Klein R, Roggendorf W (2001) Increased microglia proliferation separates pilocytic astrocytomas from diffuse astrocytomas: a double labeling study. Acta Neuropathol 101:245–248

    PubMed  CAS  Google Scholar 

  16. Matsumoto T, Fujii T, Oka KS, Hoshi TP, Sato K (1998) MIB-1 and p53 immunocytochemistry for differentiating pilocytic astrocytomas from anaplastic astrocytomas and glioblastomas in children and young adults. Histopath 33(5):446–452. doi:10.1046/j.1365-2559.1998.00503.x

    Article  CAS  Google Scholar 

  17. Scheithauer BW, Hawkins C, Tihan T, VandenBerg SR, Burger PC (2007) Pilocytic astrocytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system, 4th edn. IARC, Lyon, pp 14–21

    Google Scholar 

  18. Sharma MK, Zehnbauer BA, Watson MA, Gutmann DH (2005) RAS pathway activation and an oncogenic RAS mutation in sporadic pilocytic astrocytoma. Neurology 65(8):13335–13336. doi:10.1212/01.wnl.0000180409.78098.d7

    Article  Google Scholar 

  19. Sharma MK, Watson MA, Lyman M et al (2006) Matrilin-2 expression distinguishes clinically relevant subsets of pilocytic astrocytoma. Neurology 66(1):127–130. doi:10.1212/01.wnl.0000188667.66646.1c

    Article  PubMed  CAS  Google Scholar 

  20. Sharma MK, Mansur DB, Reifenberger G et al (2007) Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res 67(3):890–900. doi:10.1158/0008-5472.CAN-06-0973

    Article  PubMed  CAS  Google Scholar 

  21. Strother DR, Pollack IF, Fisher PG (2000) Tumors of central nervous system. In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology. Lippincott Williams and Wilkins, Philadelphia, pp 751–824

    Google Scholar 

  22. Takei H, Yogeswaren ST, Wong K et al (2008) Expression of oligodendroglial differentiation markers in pilocytic astrocytomas identifies two clinical subsets and shows a significant correlation with proliferation index and progression free survival. J Neurooncol 86:183–190. doi:10.1007/s11060-007-9455-7

    Article  PubMed  Google Scholar 

  23. Warrington NM, Woerner BM, Daginakatte GC et al (2007) Spatiotemporal differences in CXCL12 expression and cyclic AMP underlie the unique pattern of optic glioma growth in neurofibromatosis type 1. Cancer Res 67:8588–8595. doi:10.1158/0008-5472.CAN-06-2220

    Article  PubMed  CAS  Google Scholar 

  24. Wisoff JH, Abbott R, Epstein F (1990) Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. J Neurosurg 73:661–667

    Article  PubMed  CAS  Google Scholar 

  25. Wong KK, Chang YM, Tsang YT et al (2005) Expression of juvenile pilocytic astrocytomas by oligonucleotide microarrray reveals two potential subgroups. Cancer Res 65(1):76–84

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

    Kathleen M. Tibbetts, Ryan J. Emnett & David H. Gutmann

  2. Department of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA

    Feng Gao

  3. Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

    Arie Perry

  4. Department of Neurosurgery, Washington University School of Medicine, Box 8057, 660 South Euclid Avenue, St. Louis, MO, 63110, USA

    Jeffrey Russell Leonard

Authors
  1. Kathleen M. Tibbetts
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryan J. Emnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feng Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arie Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David H. Gutmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeffrey Russell Leonard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey Russell Leonard.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tibbetts, K.M., Emnett, R.J., Gao, F. et al. Histopathologic predictors of pilocytic astrocytoma event-free survival. Acta Neuropathol 117, 657–665 (2009). https://doi.org/10.1007/s00401-009-0506-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-009-0506-3

Keywords

Search

Navigation