IGF-IR: a new prognostic biomarker for human glioblastoma.
BACKGROUND
Glioblastomas (GBMs) are the most common malignant primary brain tumours in adults and are refractory to conventional therapy, including surgical resection, radiotherapy and chemotherapy. The insulin-like growth factor (IGF) system is a complex network that includes ligands (IGFI and IGFII), receptors (IGF-IR and IGF-IIR) and high-affinity binding proteins (IGFBP-1 to IGFBP-6). Many studies have reported a role for the IGF system in the regulation of tumour cell biology. However, the role of this system remains unclear in GBMs.


METHODS
We investigate the prognostic value of both the IGF ligands' and receptors' expression in a cohort of human GBMs. Tissue microarray and image analysis were conducted to quantitatively analyse the immunohistochemical expression of these proteins in 218 human GBMs.


RESULTS
Both IGF-IR and IGF-IIR were overexpressed in GBMs compared with normal brain (P<10(-4) and P=0.002, respectively). Moreover, with regard to standard clinical factors, IGF-IR positivity was identified as an independent prognostic factor associated with shorter survival (P=0.016) and was associated with a less favourable response to temozolomide.


CONCLUSIONS
This study suggests that IGF-IR could be an interesting target for GBM therapy.
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
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Maris
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
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N
D'Haene
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
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Trépant
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
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M
Le Mercier
DIAPath, Center for Microscopy and Molecular Imaging (CMMI), Académie Universitaire Wallonie-Bruxelles, Gosselies 6041, Belgium.
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Sauvage
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
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Allard
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.|DIAPath, Center for Microscopy and Molecular Imaging (CMMI), Académie Universitaire Wallonie-Bruxelles, Gosselies 6041, Belgium.
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Rorive
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.
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Demetter
DIAPath, Center for Microscopy and Molecular Imaging (CMMI), Académie Universitaire Wallonie-Bruxelles, Gosselies 6041, Belgium.|Laboratories of Image, Signal processing and Acoustics (LISA), Brussels School of Engineering/Ecole Polytechnique de Bruxelles, Université Libre de Bruxelles (ULB), Brussels 1050, Belgium.
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Decaestecker
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels 1070, Belgium.|DIAPath, Center for Microscopy and Molecular Imaging (CMMI), Académie Universitaire Wallonie-Bruxelles, Gosselies 6041, Belgium.
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Salmon
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1