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Journal of Neuro-Oncology

, Volume 122, Issue 2, pp 255–261 | Cite as

Prognostic marker analysis in pediatric intracranial ependymomas

  • Roger E. McLendonEmail author
  • Eric Lipp
  • Diane Satterfield
  • Melissa Ehinger
  • Alan Austin
  • Debra Fleming
  • Kathryn Perkinson
  • Michaela Lefaivre
  • David Zagzag
  • Benjamin Wiener
  • Sri Gururangan
  • Herbert Fuchs
  • Henry S. Friedman
  • James E. HerndonII.
  • Patrick Healy
Laboratory Investigation

Abstract

Histologic grading methods dependent upon H&E staining review have not been shown to reliably predict survival in children with intracranial ependymomas due to the subjectivity of the analytical methods. We hypothesized that the immunohistochemical detection of MIB-1, Tenascin C, CD34, VEGF, and CA IX may represent objective markers of post-operative survival (Progression Free and Overall Survival; PFS, OS) in these patients. Intracranial ependymomas from patients aged 22 years or less were studied. The original histologic grade was recorded, H&E sections were reviewed for vascular proliferation status, and immunohistochemistry was used to determine MIB-1, Tenascin C, CD34, VEGF, and CA IX status. Based upon the World Health Organization (WHO) grading system, 3 Grade I, 18 Grade II and 9 Grade III ependymomas were studied. Median follow-up time was 9.0 years; median PFS was, 6.1 years. Original WHO grade did not correlate with PFS or OS. Peri-necrotic CA IX localization correlated with PFS (Log rank = 0.0181) and OS (Log rank p = 0.0015). All patients with a CA IX ≤ 5 % total area localization were alive at last follow-up. Perinecrotic CA IX staining was also associated with vascular proliferation (p = 0.006), though not with VEGF expression score. MIB-1 labeling index (LI) correlated with OS (HR 1.06, 95 % CI 1.01, 1.12) and PFS (HR 1.08, 95 % CI 1.02, 1.14). MIB-1 LI and perinecrotic CA IX individually correlated with PFS. The effect of perinecrotic CA IX remained when grade was added to a Cox model predicting PFS. Immunodetection of CA IX and MIB-1 expression are predictive biomarkers for survival in children with posterior fossa ependymomas. These markers represent objective indicators of survival that supplement H&E grading alone.

Keywords

Pediatric Ependymoma Immunohistochemistry Vascular endothelial growth factor MIB-1 Carbonic anhydrase IX 

Notes

Acknowledgments

The authors gratefully acknowledge funding from the Pediatric Brain Tumor Foundation (REM, DS, and ME salary support). The authors also appreciate the editorial support of Ms. Bonnie Lynch. The abstract was reported in part at the 20th International Congress of Brain Tumor Research and Therapy, Lake Tahoe, California. July 20–23, 2014.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The research was performed under waiver of consent following review of the protocol by the Duke Institutional Review Board (# Pro00030787).

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Roger E. McLendon
    • 1
    Email author
  • Eric Lipp
    • 2
  • Diane Satterfield
    • 1
  • Melissa Ehinger
    • 1
  • Alan Austin
    • 1
  • Debra Fleming
    • 1
  • Kathryn Perkinson
    • 1
  • Michaela Lefaivre
    • 1
  • David Zagzag
    • 4
  • Benjamin Wiener
    • 1
  • Sri Gururangan
    • 3
  • Herbert Fuchs
    • 2
  • Henry S. Friedman
    • 2
    • 3
  • James E. HerndonII.
    • 5
  • Patrick Healy
    • 5
  1. 1.Department of PathologyDuke University School of MedicineDurhamUSA
  2. 2.Department of SurgeryDuke University School of MedicineDurhamUSA
  3. 3.Department of PediatricsDuke University School of MedicineDurhamUSA
  4. 4.Department of PathologyNew York UniversityNew YorkUSA
  5. 5.Department of BiostatisticsDuke University School of MedicineDurhamUSA

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