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

doi:10.1007/s00381-013-2142-4

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

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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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.

Originele taal-2	Engels
Pagina's (van-tot)	1253-1262
Aantal pagina's	10
Tijdschrift	Child's Nervous System
Volume	29
Nummer van het tijdschrift	8
DOI's	https://doi.org/10.1007/s00381-013-2142-4
Status	Gepubliceerd - aug. 2013
Extern gepubliceerd	Ja

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10.1007/s00381-013-2142-4

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Remke, M., Hering, E., Gerber, N. U., Kool, M., Sturm, D., Rickert, C. H., Gerß, J., Schulz, S., Hielscher, T., Hasselblatt, M., Jeibmann, A., Hans, V., Ramaswamy, V., Taylor, M. D., Pietsch, T., Rutkowski, S., Korshunov, A., Monoranu, C. M., & Frühwald, M. C. (2013). Somatostatin receptor subtype 2 (sst₂) is a potential prognostic marker and a therapeutic target in medulloblastoma. Child's Nervous System, 29(8), 1253-1262. https://doi.org/10.1007/s00381-013-2142-4

@article{dc36a4f9ae3c4e1dabc054e9f3a933f7,

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

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.",

keywords = "Children, CNS-PNET, Diagnostic imaging, Glioma, Medulloblastoma, Molecular targeting, Somatostatin receptor 2 (sst)",

author = "Marc Remke and Esther Hering and Gerber, {Nicolas U.} and Marcel Kool and Dominik Sturm and Rickert, {Christian H.} and Joachim Ger{\ss} and Stefan Schulz and Thomas Hielscher and Martin Hasselblatt and Astrid Jeibmann and Volkmar Hans and Vijay Ramaswamy and Taylor, {Michael D.} and Torsten Pietsch and Stefan Rutkowski and Andrey Korshunov and Monoranu, {Carmelia Maria} and Fr{\"u}hwald, {Michael C.}",

note = "Funding Information: Acknowledgements MF was supported by the Sonja Wasowicz Stiftung im Stifterverband f{\"u}r die Deutsche Wissenschaft and MR was supported by a postdoctoral fellowship from the Mildred Scheel Foundation.",

year = "2013",

month = aug,

doi = "10.1007/s00381-013-2142-4",

language = "English",

volume = "29",

pages = "1253--1262",

journal = "Child's Nervous System",

issn = "0256-7040",

publisher = "Springer Verlag",

number = "8",

}

Remke, M, Hering, E, Gerber, NU, Kool, M, Sturm, D, Rickert, CH, Gerß, J, Schulz, S, Hielscher, T, Hasselblatt, M, Jeibmann, A, Hans, V, Ramaswamy, V, Taylor, MD, Pietsch, T, Rutkowski, S, Korshunov, A, Monoranu, CM & Frühwald, MC 2013, 'Somatostatin receptor subtype 2 (sst₂) is a potential prognostic marker and a therapeutic target in medulloblastoma', Child's Nervous System, vol. 29, nr. 8, blz. 1253-1262. https://doi.org/10.1007/s00381-013-2142-4

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 -

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

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