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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1253-1262
Number of pages10
JournalChild's Nervous System
Volume29
Issue number8
DOIs
Publication statusPublished - Aug 2013
Externally publishedYes

Keywords

  • Children
  • CNS-PNET
  • Diagnostic imaging
  • Glioma
  • Medulloblastoma
  • Molecular targeting
  • Somatostatin receptor 2 (sst)

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