Clinical Significance of Immunohistochemical Expression of Neuropeptide Y1 Receptor in Patients with Breast Cancer in Egypt

Breast cancer (BC) is the most common malignancy in female individuals worldwide. It constitutes about 38.8% of all malignant tumors among Egyptian female individuals. Neuropeptide Y1 receptor (NPY1R) is one of the most abundant peptides in the central and peripheral nervous systems of mammals. It has been found to promote proliferation, vascularization, and stimulate migration in several cell types and tissues and some types of tumor. This the first immunohistochemical study to evaluate the expression of NPY1R in BC and its correlation with clinicopathologic parameters and patient survival. This study included 92 patients with BC. Immunohistochemical staining for NPY1R was done on paraffin-embedded formalin-fixed tissue sections. Statistically significant increases in NPY1R expression was seen in malignant (46/92; 50%) versus non-neoplastic tissue (12/29; 20.7%) (P<0.001). The receiver operating characteristic curve showed that NPY1R is a poor diagnostic test for BC (P<0.001, area under the curve=0.686) in breast tissue. Membranous was the most common pattern of positivity in carcinoma cases (24/46; 52.2%). Statistically significant associations were found between positive NPY1R expression and the presence of metastatic disease (P<0.001), clinical stage (P=0.0003), perineurial invasion (P=0.003), estrogen receptor expression (P=0.004), molecular subtype (P=0.015), Nottingham Prognostic Index risk group (P=0.04), radiotherapy treatment (P=0.01), hormonal treatment (P=0.015), and type of endocrine therapy (P=0.011). Although no significant association was detected between NPY1R-positive and NPY1R-negative cases regarding overall survival and progression-free survival, cases with non-nuclear (membranous+cytoplasmic) expression showed near significantly shorter survival (P=0.063). This study shows that NPY1R was identified in about 50% of malignant BC cases. Its expression correlates with some features of the aggressive disease being associated with metastasis, perineurial invasion, advanced stages, and poor Nottingham Prognostic Index. This suggests a potential prognostic role of NPY1R in BC. Non-nuclear expression of NPY1R seems to be more important in terms of prognosis of BC.