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

Childs Nerv Syst. 2013 Aug;29(8):1253-62. doi: 10.1007/s00381-013-2142-4. Epub 2013 May 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cerebellar Neoplasms / diagnosis*
  • Cerebellar Neoplasms / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Computational Biology
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Infant
  • Male
  • Medulloblastoma / diagnosis*
  • Medulloblastoma / genetics*
  • Neuroectodermal Tumors, Primitive / diagnosis
  • Neuroectodermal Tumors, Primitive / genetics
  • RNA, Messenger / metabolism
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*
  • Severity of Illness Index
  • Statistics as Topic
  • Statistics, Nonparametric
  • Young Adult

Substances

  • RNA, Messenger
  • Receptors, Somatostatin
  • SSTR2 protein, human