Abstract
Abstract Recent reports identified high expression of Notch 1 receptor in various tumors including adenoid cystic carcinomas (ACC). Notch 1 receptor is activated by gamma secretase cleavage to exert transcriptional control of processes including cellular differentiation and proliferation. Notch is also known to be activated in approximately 60% of T-cell acute lymphoblastic leukemias. We investigated the prevalence of Notch 1, 2 and 3 activation in different tumors by immunohistochemistry (IHC) designed separately for Notch 1, 2 and 3. Our proprietary antibodies recognize the post-gamma secretase cleavage activated Notch intracellular domain (NICD) fragments of Notch 1, Notch 2 and Notch 3, allowing direct measurement of activation of these receptors, in addition to their expression level by the tumor cells. In total we tested 48 ACCs of the salivary glands, 19 breast cancer, 35 chronic lymphocytic leukemias (CLL), 7 glioblastomas, and 35 non-small cell lung carcinomas (NSCLC) We found that at least 65% (31 out of 48) of ACCs were positive for Notch 1 activation using our assay. Of other tumor types, 4 out of 7 glioblastomas (57%), 14 out of 35 CLLs (40%), 7 out of 35 NSCLC (20%) and 2 out of 19 breast cancer cases (11%) were positive for Notch 1. Within NSCLC, 5 of the 16 tested squamous cell carcinomas were positive for Notch 1 activation (31%). Notch 2 and Notch 3 showed only rare activation in these tumors. We conclude that high levels of Notch 1 activation are identifiable in different tumor types including high prevalence in ACC, CLL and glioma. These tumors may benefit from therapeutic Notch pathway inhibition. Citation Format: Gerard Oakley, Lisa Riegle, Karim Benhadji, Andrew Schade. Prevalence of activated NOTCH receptor in solid tumors and chronic lymphocytic leukemia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1133.
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