Description:
<jats:title>Abstract</jats:title>
<jats:p>Rationale A small proportion of patients with sarcoma achieves prolonged progression free survival (PFS) with insulin growth factor type 1 receptor (IGF-1R) monoclonal antibody (Ab). A biomarker identifying in routine those patients beforehand would be useful to select patients. The aim of this study is to identify predictive factors for PFS in soft tissue sarcomas (STS), Ewing sarcoma (ES) and osteosarcoma patients receiving IGF-1R Ab. Methods The series of patients with unresecable or metastatic STS, ES, or osteosarcomas treated with IGF-1R Ab (R1507, IMC-A12, SCH 717454 and CP-751.871) in the Centre Leon Berard was studied. Tumor samples were analyzed by immunohistochemistry for expression of IGF-1R, IGFBP-3, Ki-67, HER1 and HER2. Results All tumor samples had a positive IGF-1R immunostaining on 60% to 100% of 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=3, 19%), or nuclear + cytoplasmic (n=4, 25%). Neither IGFBP-3 expression, nor Ki67 was correlated to PFS or overall survival (OS). HER2 and HER1 stainings were positive in 0 and 2 samples respectively (both primary resistant to IGF-1R Ab therapy). Exclusive intra-nuclear immunostaining for IGF-1R was significantly associated with an increased PFS (p=0.009) and OS (p=0.04). Conclusion Exclusive nuclear localization of IGF-1R in sarcomas using routine immunohistochemistry was correlated to PFS and OS after IGF1R Ab treatment in this single center series. This observation is consistent with recent data reporting that nuclear localization of IGF-1R in tumor cells is a hallmark of pathway activation.</jats:p>
<jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5578. doi:1538-7445.AM2012-5578</jats:p>