Child's Nervous System

, Volume 29, Issue 8, pp 1253–1262

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

  • Marc Remke
  • Esther Hering
  • Nicolas U. Gerber
  • Marcel Kool
  • Dominik Sturm
  • Christian H. Rickert
  • Joachim Gerß
  • Stefan Schulz
  • Thomas Hielscher
  • Martin Hasselblatt
  • Astrid Jeibmann
  • Volkmar Hans
  • Vijay Ramaswamy
  • Michael D. Taylor
  • Torsten Pietsch
  • Stefan Rutkowski
  • Andrey Korshunov
  • Carmelia-Maria Monoranu
  • Michael C. Frühwald
Original Paper

DOI: 10.1007/s00381-013-2142-4

Cite this article as:
Remke, M., Hering, E., Gerber, N.U. et al. Childs Nerv Syst (2013) 29: 1253. doi:10.1007/s00381-013-2142-4

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 sst2 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 sst2 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.

Keywords

Somatostatin receptor 2 (sst2)MedulloblastomaCNS-PNETGliomaMolecular targetingDiagnostic imagingChildren

Supplementary material

381_2013_2142_MOESM1_ESM.pptx (187 kb)
ESM 1(PPTX 187 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Marc Remke
    • 1
    • 2
    • 3
  • Esther Hering
    • 4
  • Nicolas U. Gerber
    • 5
  • Marcel Kool
    • 2
  • Dominik Sturm
    • 2
  • Christian H. Rickert
    • 6
  • Joachim Gerß
    • 7
  • Stefan Schulz
    • 8
  • Thomas Hielscher
    • 9
  • Martin Hasselblatt
    • 10
  • Astrid Jeibmann
    • 10
  • Volkmar Hans
    • 11
  • Vijay Ramaswamy
    • 1
  • Michael D. Taylor
    • 1
  • Torsten Pietsch
    • 12
  • Stefan Rutkowski
    • 13
  • Andrey Korshunov
    • 14
    • 15
  • Carmelia-Maria Monoranu
    • 16
  • Michael C. Frühwald
    • 4
    • 17
    • 18
  1. 1.Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick ChildrenUniversity of TorontoTorontoCanada
  2. 2.Division of Pediatric NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Department of Pediatric Oncology, Hematology and ImmunologyUniversity of HeidelbergHeidelbergGermany
  4. 4.Department of Pediatric Hematology and OncologyUniversity Children’s Hospital MünsterMünsterGermany
  5. 5.Department of Pediatric OncologyUniversity Children’s HospitalZürichSwitzerland
  6. 6.Institute of Neuropathology and PaidopathologyVivantes Hospitals, Friedrichshain and NeuköllnBerlinGermany
  7. 7.Department of Medical Informatics and BiomathematicsUniversity of MuensterMünsterGermany
  8. 8.Institute of Pharmacology and Toxicology Friedrich-Schiller-Universität JenaUniversity Hospitals of JenaJenaGermany
  9. 9.Division Biostatistics (C060)DKFZHeidelbergGermany
  10. 10.Institute of NeuropathologyUniversity HospitalMünsterGermany
  11. 11.Institute of NeuropathologyBethelGermany
  12. 12.Institute of NeuropathologyUniversity Hospitals BonnBonnGermany
  13. 13.Department of Pediatric Hematology and OncologyUniversity Medical Center Hamburg-EppendorfHamburg-EppendorfGermany
  14. 14.Department of NeuropathologyUniversity of HeidelbergHeidelbergGermany
  15. 15.Clinical Cooperation Unit NeuropathologyDKFZHeidelbergGermany
  16. 16.Department of Neuropathology, Institute of PathologyUniversity of WürzburgWürzburgGermany
  17. 17.Childrens’ Hospital AugsburgAugsburgGermany
  18. 18.Klinikum Augsburg, I, KinderklinikAugsburgGermany