Abstract
Objective: To assess the clinicopathological significance and molecular subtype expression of N-myc downstream regulated gene 1 (NDGR1) in invasive ductal breast carcinoma in Pakistani population.
Methodology: This study included patients who were diagnosed with invasive ductal carcinoma and underwent mastectomy or modified mastectomy at two tertiary care hospitals in Lahore. Patients who had received neoadjuvant therapy were excluded. Immunohistochemical analysis for NDRG1, ER, PR, HER2/neu, and Ki-67 was performed, and molecular subtypes were assigned accordingly. The Nottingham Prognostic Index (NPI) was calculated. Associations between NDRG1 expression and clinicopathological features were analyzed using the Chi-square test, while risk ratios were estimated for significant predictors.
Results: NDRG1 expression was statistically significant in breast carcinoma (p=0.037). The mean age of NDRG1-positive patients was 47.9±12 years. No significant association was found with age group, laterality, nodal stage, hormone receptor status, molecular subtypes, and Ki-67. Significant correlations were observed with tumor stage (p=0.044), nuclear grade (p=0.027), mitotic activity (p=0.015), and Nottingham grade (p=0.013). Patients with poor NPI had a significantly higher risk of NDRG1 positivity (RR=2.10; 95% CI: 1.18–3.73; p=0.015), and HER2 positivity was also an independent predictor (RR=2.85; 95% CI: 1.21–6.70; p=0.018). NDRG1 expression increased with higher histological grade, being highest in Grade III tumors (p=0.031).
Conclusion: NDRG1 is significantly expressed in invasive ductal carcinoma and correlates with aggressive pathological features such as higher tumor stage, mitotic activity, and Nottingham grade. However, its independent prognostic significance requires further validation through large-scale and survival-based studies.

Key words: NDRG1, breast carcinoma, HER2, Nottingham Prognostic Index, molecular subtypes.