title: Notch-1 and Notch-4 biomarker expression in triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) demonstrates lack of expression of hormone receptors and human epidermal growth factor receptor. However, there is no targeted therapy for TNBC. The authors analyzed 29 TNBC cases for Notch-1 and Notch-4 biomarker expression and subcellular location, Ki67 proliferation rate, and relevant clinical/survival data. Results demonstrated an unfavorable Ki67 rate in 90% of cases, Notch-1 expression in tumor and endothelial cells in 100% of cases, and Notch-4 expression in tumor cells in 73% of cases and endothelial cells in 100% of cases. Additionally, subcellular localization of Notch-1 and Notch-4 was predominantly nuclear and cytoplasmic. In conclusion, (a) the majority of TNBCs are high-grade infiltrating ductal carcinomas with high Ki67 proliferation rate and (b) both Notch-1 and Notch-4 receptors are overexpressed in tumor and vascular endothelial cells with subcellular localization different from that of hormone-positive breast cancer. Targeting Notch signaling with gamma secretase inhibitors should to be explored to further improve the survival rate of TNBC patients.
authors.affiliation: Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA. jspeiser@lumc.edu
authors.forename: Jodi
authors.initials: J
authors.lastname: Speiser
authors.forename: Kimberly
authors.initials: K
authors.lastname: Foreman
authors.forename: Eva
authors.initials: E
authors.lastname: Drinka
authors.forename: Constantine
authors.initials: C
authors.lastname: Godellas
authors.forename: Claudia
authors.initials: C
authors.lastname: Perez
authors.forename: Alia
authors.initials: A
authors.lastname: Salhadar
authors.forename: Çağatay
authors.initials: Ç
authors.lastname: Erşahin
authors.forename: Prabha
authors.initials: P
authors.lastname: Rajan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007087:Illinois / Q000453:epidemiology; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism*; D000074562:Receptor, Notch4; D011960:Receptors, Estrogen / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D051881:Receptor, Notch1; D000074562:Receptor, Notch4; D011960:Receptors, Estrogen; D051880:Receptors, Notch; D011980:Receptors, Progesterone; C497761:NOTCH1 protein, human; C106075:NOTCH4 protein, human