Clinical significance of Notch receptors in triple negative breast cancer¹

Article type: Research Article

Authors: Shah, Heer^a | Mistry, Mittal^a | Patel, Nupur^a | Vora, Hemangini^a;

Affiliations: [a] Immunohematology Laboratory, Cancer Biology Department, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India

Correspondence: [*] Corresponding author: Dr. Hemangini Vora, B-107 Immunohematology Laboratory, The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad – 380016, India. Tel.: 9925132020; E-mail: hemangini.vora@gcriindia.org. ORCIDs: https://orcid.org/0000-0001-9068-7608 (H. Shah); https://orcid.org/0000-0002-5820-0836 (M. Mistry); https://orcid.org/0000-0001-8165-8696 (N. Patel); https://orcid.org/0000-0003-3893-9999 (H. Vora)

Note: [ 1 ] This article received a correction notice (Erratum) post publication with DOI: 10.3233/BD-229041, available at http://doi.org/10.3233/BD-229041.

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. OBJECTIVE:To evaluate the clinical significance of Notch receptors in Triple Negative Breast Cancer. METHODS:We evaluated the association between Notch receptors and clinicopathological parameters including disease-free survival and overall survival of one hundred TNBC patients by immunohistochemistry. RESULTS:Positive expression of nuclear Notch1 receptor (18%) was found be significantly correlated with positive lymph node (p = 0.009), high BR score (p = 0.02) and necrosis (p = 0.004) while cytoplasmic expression of Notch2 receptor (26%) was significantly correlated with metastasis (p = 0.05), worse DFS (p = 0.05) and poor OS (p = 0.02) in TNBC patients. Membrane (18%) and cytonuclear (3%) Notch3 expression were significantly associated with poorly differentiated tumors (p = 0.007), high BR score (p = 0.002) and necrosis (p = 0.03) respectively. However, cytoplasmic Notch3 and Notch4 expression were negatively correlated with poor prognostic factors. CONCLUSIONS:Our data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 may serve as a potential biomarker and therapeutic target for TNBC.

Keywords: Notch receptors, Triple Negative Breast Cancer, immunohistochemistry

DOI: 10.3233/BD-220041

Journal: Breast Disease, vol. 42, no. 1, pp. 85-100, 2023