Michael J Kluk, Todd Ashworth, Hongfang Wang, Birgit Knoechel, Emily F Mason, Elizabeth A Morgan, David Dorfman, Geraldine Pinkus, Oliver Weigert, Jason L Hornick, Lucian R Chirieac, Michelle Hirsch, David J Oh, Andrew P South, Irene M Leigh, Celine Pourreyron, Andrew J Cassidy, Daniel J Deangelo, David M Weinstock, Ian E Krop, Deborah Dillon, Jane E Brock, Alexander J F Lazar, Myron Peto, Raymond J Cho, Alexander Stoeck, Brian B Haines, Sriram Sathayanrayanan, Scott Rodig, Jon C Aster
Fixed, paraffin-embedded (FPE) tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1) in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC) stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies...
2013: PloS One