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Somatostatin receptor subtype 2 (sst2) is a potential prognostic marker and a therapeutic target in medulloblastoma

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Abstract

Introduction

Neuroectodermal tumors in general demonstrate high and dense expression of the somatostatin receptor subtype 2 (sst2). It controls proliferation of both normal and neoplastic cells. sst2 has thus been suggested as a therapeutic target and prognostic marker for certain malignancies.

Methods

To assess global expression patterns of sst 2 mRNA, we evaluated normal (n = 353) and tumor tissues (n = 340) derived from previously published gene expression profiling studies. These analyses demonstrated specific upregulation of sst 2 mRNA in medulloblastoma (p < 0.001). sst2 protein was investigated by immunohistochemistry in two independent cohorts.

Results

Correlation of sst2 protein expression with clinicopathological variables revealed significantly higher levels in medulloblastoma (p < 0.05) compared with CNS-PNET, ependymoma, or pilocytic astrocytoma. The non-SHH medulloblastoma subgroup tumors showed particularly high expression of sst2, when compared to other tumors and normal tissues. Furthermore, we detected a significant survival benefit in children with tumors exhibiting high sst2 expression (p = 0.02) in this screening set. A similar trend was observed in a validation cohort including 240 independent medulloblastoma samples.

Conclusion

sst2 is highly expressed in medulloblastoma and deserves further evaluation in the setting of prospective trials, given its potential utility as a prognostic marker and a therapeutic target.

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Acknowledgements

MF was supported by the Sonja Wasowicz Stiftung im Stifterverband für die Deutsche Wissenschaft and MR was supported by a postdoctoral fellowship from the Mildred Scheel Foundation.

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Authors and Affiliations

  1. Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Marc Remke, Vijay Ramaswamy & Michael D. Taylor

  2. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Marc Remke, Marcel Kool & Dominik Sturm

  3. Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany

    Marc Remke

  4. Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster, Münster, Germany

    Esther Hering & Michael C. Frühwald

  5. Department of Pediatric Oncology, University Children’s Hospital, Zürich, Switzerland

    Nicolas U. Gerber

  6. Institute of Neuropathology and Paidopathology, Vivantes Hospitals, Friedrichshain and Neukölln, Berlin, Germany

    Christian H. Rickert

  7. Department of Medical Informatics and Biomathematics, University of Muenster, Münster, Germany

    Joachim Gerß

  8. Institute of Pharmacology and Toxicology Friedrich-Schiller-Universität Jena, University Hospitals of Jena, Jena, Germany

    Stefan Schulz

  9. Division Biostatistics (C060), DKFZ, Heidelberg, Germany

    Thomas Hielscher

  10. Institute of Neuropathology, University Hospital, Münster, Germany

    Martin Hasselblatt & Astrid Jeibmann

  11. Institute of Neuropathology, Bethel, Germany

    Volkmar Hans

  12. Institute of Neuropathology, University Hospitals Bonn, Bonn, Germany

    Torsten Pietsch

  13. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Germany

    Stefan Rutkowski

  14. Department of Neuropathology, University of Heidelberg, Heidelberg, Germany

    Andrey Korshunov

  15. Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany

    Andrey Korshunov

  16. Department of Neuropathology, Institute of Pathology, University of Würzburg, Würzburg, Germany

    Carmelia-Maria Monoranu

  17. Childrens’ Hospital Augsburg, Augsburg, Germany

    Michael C. Frühwald

  18. Klinikum Augsburg, I, Kinderklinik, Stenglinstr. 2, 86156, Augsburg, Germany

    Michael C. Frühwald

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  1. Marc Remke
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  2. Esther Hering
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  3. Nicolas U. Gerber
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  14. Michael D. Taylor
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  16. Stefan Rutkowski
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  19. Michael C. Frühwald
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Corresponding author

Correspondence to Michael C. Frühwald.

Additional information

Marc Remke, Esther Hering, and Nicolas U. Gerber contributed equally to this work

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Remke, M., Hering, E., Gerber, N.U. et al. Somatostatin receptor subtype 2 (sst2) is a potential prognostic marker and a therapeutic target in medulloblastoma. Childs Nerv Syst 29, 1253–1262 (2013). https://doi.org/10.1007/s00381-013-2142-4

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  • DOI: https://doi.org/10.1007/s00381-013-2142-4

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