TY - JOUR
T1 - Somatostatin receptor subtype 2 (sst2) is a potential prognostic marker and a therapeutic target in medulloblastoma
AU - Remke, Marc
AU - Hering, Esther
AU - Gerber, Nicolas U.
AU - Kool, Marcel
AU - Sturm, Dominik
AU - Rickert, Christian H.
AU - Gerß, Joachim
AU - Schulz, Stefan
AU - Hielscher, Thomas
AU - Hasselblatt, Martin
AU - Jeibmann, Astrid
AU - Hans, Volkmar
AU - Ramaswamy, Vijay
AU - Taylor, Michael D.
AU - Pietsch, Torsten
AU - Rutkowski, Stefan
AU - Korshunov, Andrey
AU - Monoranu, Carmelia Maria
AU - Frühwald, Michael C.
N1 - Funding Information:
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.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Children
KW - CNS-PNET
KW - Diagnostic imaging
KW - Glioma
KW - Medulloblastoma
KW - Molecular targeting
KW - Somatostatin receptor 2 (sst)
UR - http://www.scopus.com/inward/record.url?scp=84880788029&partnerID=8YFLogxK
U2 - 10.1007/s00381-013-2142-4
DO - 10.1007/s00381-013-2142-4
M3 - Article
AN - SCOPUS:84880788029
SN - 0256-7040
VL - 29
SP - 1253
EP - 1262
JO - Child's Nervous System
JF - Child's Nervous System
IS - 8
ER -