Child's Nervous System, 2013, Vol.29(8), pp.1253-1262
Byline: Marc Remke (1,2,3), Esther Hering (4), Nicolas U. Gerber (5), Marcel Kool (2), Dominik Sturm (2), Christian H. Rickert (6), Joachim Gerss (7), Stefan Schulz (8), Thomas Hielscher (9), Martin Hasselblatt (10), Astrid Jeibmann (10), Volkmar Hans (11), Vijay Ramaswamy (1), Michael D. Taylor (1), Torsten Pietsch (12), Stefan Rutkowski (13), Andrey Korshunov (14,15), Carmelia-Maria Monoranu (16), Michael C. Fruhwald (4,17,18) Keywords: Somatostatin receptor 2 (sst.sub.2); Medulloblastoma; CNS-PNET; Glioma; Molecular targeting; Diagnostic imaging; Children Abstract: Introduction Neuroectodermal tumors in general demonstrate high and dense expression of the somatostatin receptor subtype 2 (sst.sub.2). It controls proliferation of both normal and neoplastic cells. sst.sub.2 has thus been suggested as a therapeutic target and prognostic marker for certain malignancies. Methods To assess global expression patterns of sst .sub.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 .sub.2 mRNA in medulloblastoma (p〈0.001). sst.sub.2 protein was investigated by immunohistochemistry in two independent cohorts. Results Correlation of sst.sub.2 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 sst.sub.2, when compared to other tumors and normal tissues. Furthermore, we detected a significant survival benefit in children with tumors exhibiting high sst.sub.2 expression (p=0.02) in this screening set. A similar trend was observed in a validation cohort including 240 independent medulloblastoma samples. Conclusion sst.sub.2 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. Author Affiliation: (1) 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 (2) Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany (3) Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany (4) Department of Pediatric Hematology and Oncology, University Children's Hospital Munster, Munster, Germany (5) Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland (6) Institute of Neuropathology and Paidopathology, Vivantes Hospitals, Friedrichshain and Neukolln, Berlin, Germany (7) Department of Medical Informatics and Biomathematics, University of Muenster, Munster, Germany (8) Institute of Pharmacology and Toxicology Friedrich-Schiller-Universitat Jena, University Hospitals of Jena, Jena, Germany (9) Division Biostatistics (C060), DKFZ, Heidelberg, Germany (10) Institute of Neuropathology, University Hospital, Munster, Germany (11) Institute of Neuropathology, Bethel, Germany (12) Institute of Neuropathology, University Hospitals Bonn, Bonn, Germany (13) Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Germany (14) Department of Neuropathology, University of Heidelberg, Heidelberg, Germany (15) Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany (16) Department of Neuropathology, Institute of Pathology, University of Wurzburg, Wurzburg, Germany (17) Childrens' Hospital Augsburg, Augsburg, Germany (18) Klinikum Augsburg, I, Kinderklinik, Stenglinstr. 2, 86156, Augsburg, Germany Article History: Registration Date: 01/05/2013 Received Date: 25/03/2013 Accepted Date: 30/04/2013 Online Date: 16/05/2013 Article note: Marc Remke, Esther Hering, and Nicolas U. Gerber contributed equally to this work Electronic supplementary material The online version of this article (doi: 10.1007/s00381-013-2142-4) contains supplementary material, which is available to authorized users.
Somatostatin receptor 2 (sst) ; Medulloblastoma ; CNS-PNET ; Glioma ; Molecular targeting ; Diagnostic imaging ; Children
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