Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas.
Eur J Cancer
; 48(16): 3027-35, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-22682017
ABSTRACT
AIMS:
A minority of patients with advanced sarcoma achieve prolonged progression free survival (PFS) with insulin growth factor type 1 receptor (IGF-1R) monoclonal antibody (Ab) therapy. A biomarker identifying those patients beforehand would be useful to select patients for the development of these agents.METHODS:
This single centre series includes patients with unresectable or metastatic soft tissue sarcomas (STS), Ewing sarcoma (ES) and osteosarcoma treated with IGF-1R Ab (R1507, IMC-A12, SCH 717454 and CP-751.871) in the Centre Léon Bérard. Tumour samples were analysed by immunohistochemistry for expression of IGF-1R, insulin-like growth factor binding protein type 3 (IGFBP-3), Ki67, epidermal growth factor receptor (HER1) and human epidermal growth factor receptor 2 (HER2). Predictive factors for PFS and overall survival (OS) were investigated.RESULTS:
All tumour samples had a positive IGF-1R immunostaining on 60% to 100% of tumour cells. IGFBP-3 immunostaining was observed in 12 (75%) samples with 5% to 100% of positive cells. IGF-1R immunostaining was nuclear (n=9, 56%), cytoplasmic (n=4, 25%), or nuclear +cytoplasmic (n=3, 19%). Neither IGFBP-3 expression, nor Ki67 was correlated to PFS. HER2 and HER1 staining were positive in 0 and 2 samples respectively (both primary resistant to IGF-1R Ab therapy). Exclusive intra-nuclear immunoreactivity for IGF-1R was significantly associated with a better PFS (p=0.01) and OS (p=0.007).CONCLUSION:
Exclusive nuclear localisation of IGF-1R is an easily testable biomarker associated with a better PFS and OS for patients treated with IGF-1R Ab therapy. Nuclear localisation of IGF-1R in tumour cells might be a hallmark of pathway activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma
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Imuno-Histoquímica
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Biomarcadores Tumorais
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Núcleo Celular
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Receptor IGF Tipo 1
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Anticorpos Monoclonais
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article