Abstract
Ovarian cancer (OC) is among the most lethal cancer among all gynaecological malignancies. Since most OC patients are diagnosed only at advanced stages mainly because of their imperceptible/nonspecific symptoms, survival rates are low. Therefore, more molecular biomarkers are needed to achieve more effective molecular stratification for better prognostic and theranostic outcomes. The cadherin family, particularly N-cadherin (N-CAD; also known as CDH2), is critical for cell-cell adhesion and epithelial- mesenchymal transition (EMT) of cancer. N-CAD protein has also been shown to be overexpressed in many advanced carcinomas. The aim of this study was to investigate the expression patterns of N-CAD protein, determine their correlations with the clinicopathological features of OC patients, and evaluate its prognostic value and involvement in EMT and metastasis. Protein expression of N-CAD was studied in 117 formalin-fixed and paraffin-embedded (FFPE) blocks from patients diagnosed with OC using Tissue Microarray and immunohistochemistry techniques. The N-CAD protein was overexpressed in 58% of our OC cohort. Furthermore, its cytoplasmic overexpression was significantly correlated with tumor grade (p= 0.05), tumor subtype (p= 0.05), tumor necrosis (p= 0.01), and age at menarche (p= 0.002). Interestingly, Kaplan-Meier analysis showed a significant correlation of disease-free survival (DFS) with OC patients with cytoplasmic N-CAD overexpression (p< 0.03, log rank). Patients with high N-CAD expression have approximately twice the recurrence rate at 5-year follow-up. The results of this study demonstrate a poor prognostic role of N-CAD overexpression in OC, which is reflected in higher recurrence and death rates of OC and its molecular contribution to EMT and distant metastasis. Therefore, OC patients with overexpressed N-CAD need to be monitored more frequently and closely. Further studies with larger patient cohorts are needed to validate these findings, demystify the role of N-CAD in OC pathophysiology, and further investigate its role as a potential therapeutic target.