- 作者：Ir¨¨ne Asmane ; Emmanuel Watkin ; Laurent Alberti ; Adeline Duc ; Perrine Marec-Berard ; Isabelle Ray-Coquard ; Philippe Cassier ; Anne-Val¨¦rie Decouvelaere ; Dominique Ranch¨¨re ; Jean-Emmanuel Kurtz ; Jean-Pierre Bergerat ; Jean-Yves Blay
- 关键词：Sarcoma ; Nuclear IGF-1R ; IGF-1R monoclonal antibody
- 刊名：European Journal of Cancer
- 出版年：2012
- 出版时间：November, 2012
- 年：2012
- 卷：48
- 期：16
- 页码：3027-3035
- 全文大小：1129 K
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 L¨¦on B¨¦rard. 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.