Prognostic Subcellular Notch2, Notch3 and Jagged1 Localization Patterns in Early Triple-negative Breast Cancer.

Prognostic Subcellular Notch2, Notch3 and Jagged1 Localization Patterns in Early Triple-negative Breast Cancer.

Anticancer research (2017-05-10)

Titika-Marina Strati, Vassiliki Kotoula, Ioannis Kostopoulos, Kyriaki Manousou, Christos Papadimitriou, Georgios Lazaridis, Sotiris Lakis, George Pentheroudakis, Dimitrios Pectasides, Elissavet Pazarli, Christos Christodoulou, Evangelia Razis, Kitty Pavlakis, Christina Magkou, Sofia Chrisafi, Gerasimos Aravantinos, Dimitrios Bafaloukos, Pavlos Papakostas, Helen Gogas, Konstantine T Kalogeras, George Fountzilas

PMID28476798

ABSTRACT

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. 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. 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). Specific Notch3 and Jag1 subcellular localization patterns may provide clues for the behavior of the tumors and potentially for Jag1 targeting in TNBC patients.

MATERIALS

Product Number

Brand

Product Description

HPA021555

Sigma-Aldrich

Anti-JAG1 antibody produced in rabbit, Prestige Antibodies^® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution