INTERPLAY OF SNAIL/SLUG, AND NEUROPILIN-2 WITH HISTOPATHOLOGICAL AND HORMONAL FACTORS IN PREDICTING LYMPH NODE METASTASIS IN INVASIVE DUCTAL CARCINOMA - A RETROSPECTIVE STUDY

Abstract

Background: Invasive ductal carcinoma (IDC) is the most prevalent histological subtype of breast cancer and is characterized by marked biological heterogeneity. Epithelial-mesenchymal transition (EMT)-related proteins, including SNAIL/SLUG, and Neuropilin-2 (NRP2), have been implicated in tumor invasion, progression, and metastatic dissemination. Aim: To evaluate the immunohistochemical expression of SNAIL/SLUG, and NRP2 in invasive ductal carcinoma and to investigate their association with lymph node metastasis, clinicopathological characteristics, and hormonal receptor status. Materials and Methods: A retrosepective observational study was conducted on 80 patients with histopathologically confirmed invasive ductal carcinoma who underwent mastectomy between January 2022 and December 2025. Immunohistochemical staining for SNAIL/SLUG and NRP2 was performed, and expression patterns were correlated with tumor grade, lymph node status, estrogen receptor (ER), progesterone receptor (PR), HER2/neu status, and Ki-67 proliferative index. Results: Among 80 invasive ductal carcinoma cases, high NRP2 and SNAIL/SLUG expression was observed in 27.5% and 40.0% of tumors, respectively. Significant co-expression of both markers was demonstrated (OR=7.00, p<0.001), with a positive correlation between their numerical expression scores (ρ=0.372, p<0.001). High SNAIL/SLUG expression was significantly associated with ER negativity (57.1% vs 26.7%, p=0.011). NRP2 expression was higher in node-positive tumors, although the association was not statistically significant. Both markers showed higher expression in triple-negative tumors. Conclusion: NRP2 and SNAIL/SLUG demonstrate significant biological interplay in invasive ductal carcinoma and may contribute to aggressive tumor behavior. Their association with ER negativity and increased expression in triple-negative tumors suggests potential value as biomarkers of aggressive disease and lymphatic metastatic potential. Further larger scale studies are warranted to establish their independent prognostic and predictive significance.