Clinical & Experimental Metastasis

, Volume 23, Issue 1, pp 55–63

Heparanase Expression and TrkC/p75NTR Ratios in Human Medulloblastoma

  • Neeta D. Sinnappah-Kang
  • Robert E. Mrak
  • Daniel B. Paulsen
  • Dario Marchetti
Original paper

DOI: 10.1007/s10585-006-9017-y

Cite this article as:
Sinnappah-Kang, N.D., Mrak, R.E., Paulsen, D.B. et al. Clin Exp Metastasis (2006) 23: 55. doi:10.1007/s10585-006-9017-y

Abstract

Medulloblastoma (MB), the most devastating and common brain tumor in children, is highly invasive and extremely difficult to treat. Identifying the properties of MB tumors that cause them to invade and metastasize is therefore imperative for the development of novel treatments. We performed investigations to elucidate prognostic implications of heparanase (HPSE-1) and TrkC/p75NTR expression in MB using formalin-fixed, paraffin-embedded (FFPE) MB clinical specimens from children aged 1–19 years. Expressions of p75NTR and HPSE-1 correlated with each other (Pearson’s correlation R = 0.899; P < 0.0001; R2 = 81%; n = 14). In addition, TrkC:p75NTR ratios correlated with MB meningeal spread (R = 0.608; P = 0.0212; R2 = 37%; n = 14). Secondly, using antibodies specific to TrkC and HPSE-1, we carried out immunohistochemistry (IHC) on 22 human MB tissue samples. IHC reaction scores revealed a significant expression of HPSE-1 in 76% of MB tissues from children aged 3 years and older (P = 0.0490; n = 17) while TrkC immunoreactivity was detected in 71% of these patient samples. Of note, TrkC was significantly present in 100% of MB female patients (P = 0.0313; n = 6). These studies support the role of p75NTR and HPSE-1 as two novel molecular determinants involved in the biology and clinical progression of MB.

Keywords

Formalin-fixed paraffin-embedded tumors Heparanase Human medulloblastoma p75NTR Real-time PCR TrkC 

Abbreviations

BM

basement membrane

CSF

cerebrospinal fluid

Ct

threshold value

ECM

extracellular matrix

FAM

carboxyfluorescein

FFPE

formalin-fixed paraffin-embedded

HPSE-1

heparanase

HRP

horseradish peroxidase

HSPG

heparan sulfate proteoglycans

IHC

immunohistochemistry

MB

medulloblastoma

MRI

magnetic resonance imaging

QPCR

quantitative polymerase chain reaction

TAMRA

n,n,n′,n′-tetramethyl-6-carboxyrhodamine

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Neeta D. Sinnappah-Kang
    • 1
  • Robert E. Mrak
    • 3
  • Daniel B. Paulsen
    • 4
  • Dario Marchetti
    • 2
  1. 1.Division of PediatricsUniversity of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Comparative Biomedical Sciences, School of Veterinary MedicineLouisiana State University – Baton RougeBaton RougeUSA
  3. 3.Department of PathologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  4. 4.Department of Pathobiological Sciences, School of Veterinary MedicineLouisiana State University – Baton RougeBaton Rouge USA

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