NEURAL EPIDERMAL GROWTH FACTOR-LIKE 1 (NELL1) EXPRESSION AND THE NOTTINGHAM PROGNOSTIC INDEX IN BREAST CARCINOMA: A CROSS-SECTIONAL STUDY FROM PAKISTAN

Abstract

Breast carcinoma remains a major cause of cancer-related morbidity and mortality, particularly in resource-limited settings where prognostic assessment relies largely on histopathology and immunohistochemistry. Neural epidermal growth factor-like 1 (NELL1) is a secreted glycoprotein with emerging but incompletely defined relevance in tumour biology. This cross-sectional observational study evaluated NELL1 protein expression in breast carcinoma and assessed its association with the Nottingham Prognostic Index (NPI) and selected clinicopathological parameters. The study was conducted at the Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan, from May 2025 to October 2025. A total of 128 histologically confirmed breast carcinoma cases were included using consecutive sampling. NELL1 immunohistochemistry was performed on formalin-fixed paraffin embedded tissue sections, and staining was interpreted using the Allred scoring system; scores of 0–2 were considered negative, whereas scores of 3–8 were considered positive. NELL1 immunoreactivity was observed in 108 cases (84.4%), while 20 cases (15.6%) were negative. Mild, moderate, and strong staining intensities were observed in 37 (28.9%), 37 (28.9%), and 34 (26.6%) cases, respectively. NELL1 expression showed significant associations with tumour stage (P<0.001), lymph node involvement (P=0.002), and NPI category (P<0.001). No significant association was observed with tumour size, histological grade, surgical margin status, lymphovascular invasion, or distant metastasis. These findings suggest that NELL1 expression may be associated with adverse clinicopathological features and poorer NPI categorization in breast carcinoma, especially where expanded molecular testing is not routinely available. Further validation with molecular subtyping and outcome-based data is required.