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Heparanase Expression and TrkC/p75NTR Ratios in Human Medulloblastoma

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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; R 2 = 81%; n = 14). In addition, TrkC:p75NTR ratios correlated with MB meningeal spread (R = 0.608; P = 0.0212; R 2 = 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.

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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

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Acknowledgements

We would like to thank Dr. Manjit S. Kang, Professor of Quantitative Genetics (LSU-AgCtr) for his help with SAS analyses and for reviewing the manuscript. We would also like to thank Julie Miller and Sherry Ring (LSU-SVM) for their help in performing the immunoreactions. We also express our gratitude to Adam J. Kaiser for his help in processing tissue samples and to Bryan E. Blust for his editorial help. This work was supported by grants from National Institutes of Health of USA (NIH) (R21 CA103955) and from Phillip Morris USA and Phillip Morris International to D.M.

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Authors and Affiliations

  1. Division of Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Neeta D. Sinnappah-Kang

  2. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University – Baton Rouge, Baton Rouge, LA , 70803, USA

    Dario Marchetti

  3. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR , 72223, USA

    Robert E. Mrak

  4. Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University – Baton Rouge, Baton Rouge , LA, 70803, USA

    Daniel B. Paulsen

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  1. Neeta D. Sinnappah-Kang
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  2. Robert E. Mrak
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  3. Daniel B. Paulsen
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  4. Dario Marchetti
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Correspondence to Dario Marchetti.

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Sinnappah-Kang, N.D., Mrak, R.E., Paulsen, D.B. et al. Heparanase Expression and TrkC/p75NTR Ratios in Human Medulloblastoma. Clin Exp Metastasis 23, 55–63 (2006). https://doi.org/10.1007/s10585-006-9017-y

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  • DOI: https://doi.org/10.1007/s10585-006-9017-y

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