Carsten Friedrich1, André O von Bueren2,3,4, Larissa Kolevatova5, Christian Bernreuther5, Tobias Grob6, Diego Sepulveda-Falla5, Leander van den Boom7, Manfred Westphal7, Ronald Simon6, Markus Glatzel8. 1. Division of Pediatric Oncology, Hematology and Hemostaseology, Department of Woman's and Children's Health, University Hospital Leipzig, Leipzig, Germany. 2. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 3. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany. 4. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Hospital of Geneva, Geneva, Switzerland. 5. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany. 6. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 7. Department of Neurological Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 8. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany. m.glatzel@uke.de.
Abstract
PURPOSE: The aim of this study was to investigate the epidermal growth factor receptor (EGFR) status in ependymoma specimens, as there is a need for new prognostic and druggable targets in this disease. METHODS: Ependymomas (WHO grade II, n = 40; WHO grade III, n = 15) located spinal (n = 35), infratentorial (n = 14), and supratentorial (n = 6) of 53 patients with a median age of 40 (range, 2-79) years were analyzed for Ki-67, p53, and EGFR expression by immunohistochemistry using a tissue microarray and for EGFR gene copy number alterations/mutations. Results were correlated to clinical data. RESULTS: EGFR overexpression was found in 30/60% of ependymomas depending on the antibody used and was more pronounced in WHO grade III. High EGFR gene copy number gains were found in 6 (11%) ependymomas with half of them being amplifications. EGFR amplified ependymomas displayed an EGFR overexpression with both antibodies in two of three cases. A missense mutation in exon 20 of EGFR (S768I) was detected in one amplified case. CONCLUSIONS: EGFR is frequently overexpressed in ependymomas. Other mechanisms than amplification of the EGFR gene appear to contribute to EGFR overexpression in most cases. EGFR mutations may be present in a small subset of ependymomas.
PURPOSE: The aim of this study was to investigate the epidermal growth factor receptor (EGFR) status in ependymoma specimens, as there is a need for new prognostic and druggable targets in this disease. METHODS:Ependymomas (WHO grade II, n = 40; WHO grade III, n = 15) located spinal (n = 35), infratentorial (n = 14), and supratentorial (n = 6) of 53 patients with a median age of 40 (range, 2-79) years were analyzed for Ki-67, p53, and EGFR expression by immunohistochemistry using a tissue microarray and for EGFR gene copy number alterations/mutations. Results were correlated to clinical data. RESULTS:EGFR overexpression was found in 30/60% of ependymomas depending on the antibody used and was more pronounced in WHO grade III. High EGFR gene copy number gains were found in 6 (11%) ependymomas with half of them being amplifications. EGFR amplified ependymomas displayed an EGFR overexpression with both antibodies in two of three cases. A missense mutation in exon 20 of EGFR (S768I) was detected in one amplified case. CONCLUSIONS:EGFR is frequently overexpressed in ependymomas. Other mechanisms than amplification of the EGFR gene appear to contribute to EGFR overexpression in most cases. EGFR mutations may be present in a small subset of ependymomas.
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