Clinical Significance of Notch Receptors In Triple Negative Breast Cancer

Abstract

Background: The Notch signaling pathway is an evolutionary conserved cell signaling pathway that plays an indispensable role in essential developmental processes. Aberrant activation of Notch pathway is known to initiate wide array of diseases and cancers. The role of Notch receptors and the effect of their expression in Triple Negative Breast Cancer is unknown. Methods and Results: In this study, we evaluated the association between Notch receptors and clinicopathological parameters including disease-free survival and overall survival of one hundred TNBC patients by immunohistochemistry. We observed membrane, cytoplasmic and nuclear localization of Notch receptors in tumor cells of TNBC patients. It was observed that positive expression of nuclear Notch1 receptor (18%) was found be significantly correlated with high BR score (p=0.009) and necrosis (p=0.003) while cytoplasmic expression of Notch2 receptor (26%) was significantly correlated with local or distant metastasis (p=0.04), worse DFS (p=0.05) and poor OS (p=0.02) in TNBC patients. Further, it was determined that cytoplasmic (65%) and cytonuclear (3%) expression of Notch3 was significantly associated with poorly differentiated tumors (p=0.008) and necrosis (p=0.04) respectively. However, cytoplasmic Notch3 and Notch4 expression were negatively correlated with poor prognostic factors. Conclusion: Our data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 receptor may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 receptor may serve as a potential biomarker and therapeutic target for TNBC.