Immunohistochemical expression of Neurogenic Locus Notch Homolog 4 (Notch4) in invasive breast carcinoma: Correlation with clinicopathological parameters and immunohistochemical-based subtypes

Abstract

IntroductionStarting out with its discovery as small notches on fly wings, Neurogenic Locus Notch Homolog 4 (Notch4) signaling has been sparked as unique pathway implicated in cellular multiplication, differentiation, and regulation of stem cells. Its aberrant activation causes arrays of cancers including breast cancer. ObjectivesThe aim of the present study was to evaluate the immunohistochemical expression level of Notch4 and its subcellular localization in invasive breast carcinoma. The correlation between Notch4 expression and both of clinicopathological parameters and immunohistochemical-based subtypes of studied cases was also assessed. Methods and materialsImmunohistochemical expression of Notch4 receptor was examined in 60 specimens of paraffin-embedded sections of invasive breast cancer. Normal and hyperplastic breast tissue adjacent to carcinoma cells was also included in the study. ResultsThere was a significant increase in the expression level of Notch4 protein in breast cancer, compared to that of normal breast tissue and hyperplastic breast lesions. Also, there was a statistical significant correlation between Notch4 expression level and tumor size, tumor grade, nodal metastasis, lymphovascular invasion, human epidermal growth factor receptor 2 (her2) status, Her2-enriched and triple negative subtypes, and Ki67. Furthermore, an inverse significant correlation was found between Notch4 expression and both of age and estrogen receptor (ER). No statistical significant correlation was found between Notch4 expression and tumor histological subtypes, Tumor infiltrating lymphocytes (TILs), and fibrosis. ConclusionNotch4 overexpression has been implicated in breast cancer development, progression and emergence of aggressive biological phenotypes.