title: Somatostatin receptor subtype 2 (sst₂) is a potential prognostic marker and a therapeutic target in medulloblastoma.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.forename: Esther
authors.initials: E
authors.lastname: Hering
authors.forename: Nicolas U
authors.initials: NU
authors.lastname: Gerber
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.forename: Dominik
authors.initials: D
authors.lastname: Sturm
authors.forename: Christian H
authors.initials: CH
authors.lastname: Rickert
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerß
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: Astrid
authors.initials: A
authors.lastname: Jeibmann
authors.forename: Volkmar
authors.initials: V
authors.lastname: Hans
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramaswamy
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Carmelia-Maria
authors.initials: CM
authors.lastname: Monoranu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Frühwald
mesh_terms: D000293:Adolescent; D002528:Cerebellar Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019295:Computational Biology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis* / Q000235:genetics*; D018242:Neuroectodermal Tumors, Primitive / Q000175:diagnosis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human