@article{3087087, title = "Prognostic subcellular Notch2, Notch3 and Jagged1 localization patterns in early triple-negative breast cancer", author = "Strati, T.-M. and Kotoula, V. and Kostopoulos, I. and Manousou, K. and Papadimitriou, C. and Lazaridis, G. and Lakis, S. and Pentheroudakis, G. and Pectasides, D. and Pazarli, E. and Christodoulou, C. and Razis, E. and Pavlakis, K. and Magkou, C. and Chrisafi, S. and Aravantinos, G. and Bafaloukos, D. and Papakostas, P. and Gogas, H. and Kalogeras, K.T. and Fountzilas, G.", journal = "ANTICANCER RESEARCH", year = "2017", volume = "37", number = "5", pages = "2323-2334", publisher = "International Institute of Anticancer Research", issn = "0250-1291", doi = "10.21873/anticanres.11570", keywords = "anthracycline; epidermal growth factor receptor 2; estrogen receptor; Notch2 receptor; Notch3 receptor; P cadherin; progesterone receptor; protein Jagged 1; protein p53; uvomorulin; antineoplastic agent; JAG1 protein, human; NOTCH2 protein, human; Notch2 receptor; NOTCH3 protein, human; Notch3 receptor; protein Jagged 1, adjuvant radiotherapy; adult; aged; antigen antibody complex; Article; cancer chemotherapy; cancer hormone therapy; cancer prognosis; cancer radiotherapy; cancer survival; cell adhesion; cellular distribution; disease free survival; down regulation; female; fluorescence in situ hybridization; follow up; human; immunohistochemistry; lymphocytic infiltration; major clinical study; modified radical mastectomy; multimodality cancer therapy; overall survival; partial mastectomy; priority journal; protein expression; protein localization; retrospective study; translational research; treatment outcome; triple negative breast cancer; tumor associated leukocyte; tumor volume; cell membrane; cell nucleus; cytoplasm; metabolism; middle aged; prognosis; Triple Negative Breast Neoplasms, Anthracyclines; Antineoplastic Agents; Cell Membrane; Cell Nucleus; Cytoplasm; Female; Humans; Jagged-1 Protein; Middle Aged; Prognosis; Receptor, Notch2; Receptor, Notch3; Triple Negative Breast Neoplasms", abstract = "Background: The Notch pathway has been implicated in triple-negative breast cancer (TNBC). Herein, we studied the subcellular localization of the less investigated Notch2 and Notch3 and that of the Jagged1 (Jag1) ligand in patients with operable TNBC. Patients and Methods: We applied immunohistochemistry for Notch2, Notch3 and Jag1 in 333 tumors from TNBC patients treated with adjuvant anthracycline-based chemotherapy. We evaluated cytoplasmic (c), membranous (m) and nuclear (n) protein localization. Results: c-Notch2 (35% positive tumors), c-Notch3 (63%), c-Jag1 (43%), m-Notch3 (23%) and n-Jag1 (17%) were analyzed individually and by using hierarchical clustering for prognostic evaluation. Upon multivariate analysis, compared to high m-Notch3 in the absence of n-Jag1 (cluster 4), all other marker combinations (clusters 1, 2, 3) conferred significantly higher risk for relapse (p<0.05). Conclusion: Specific Notch3 and Jag1 subcellular localization patterns may provide clues for the behavior of the tumors and potentially for Jag1 targeting in TNBC patients." }