Abstract
Abstract Purpose: Endoglin/CD105 is a homodimeric transmembrane glycoprotein that is expressed on the proliferating endothelium of solid tumors. TRC105, the chimeric IgG1 antibody with high affinity binding for human CD105, has recently undergone human testing. This exploratory study sought to validate CD105 as a potential therapeutic target in sarcomas. Methods: We performed immunohistochemical staining for CD105 expression in 146 retrospectively identified paraffin embedded sarcoma patient samples in our tumor registry, utilizing an anti-CD105 antibody (clone 4G11, Novocastra). The diagnoses were verified and samples were examined for CD105 expression in the malignant vasculature as well as tumor cells. Results: The vast majority of specimen expressed CD105 in the tumor vasculature, 134 of 137 evaluable cases. CD105 expression in the cells of the varied sarcoma histologies themselves were as follows: 19/20 angiosarcomas, 6/7 Ewing sarcomas, 8/20 undifferentiated pleomorphic sarcomas, 6/20 uterine leiomyosarcomas (LMS), 4/20 osteosarcomas, 3/20 non-uterine LMS, 3/20 synovial sarcomas. None of the 19 evaluated chondrosarcoma cells expressed CD105. Thirteen of 19 angiosarcomas showed CD105 expression in >50% of tumor cells, 3 of 19 showed CD105 expression in 25-49% of the tumor cells and 3 of 19 showed CD105 expression in 5-24% of tumor cells. Conclusions: CD105 targeting appears to be a rational antiangiogenic therapeutic approach in sarcomas, with particular emphasis on angiosarcomas. A clinical trial utilizing TRC105 in soft tissue sarcomas is currently under development. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B237. Citation Format: Karen Fritchie, Steven Attia, Scott Okuno, Carola Arndt, Steven Robinson. CD105: A therapeutic target for sarcomas. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B237.
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