Protein expression of Notch-1 and Notch-3 behaves differently in oral squamous cell carcinoma

Objective: Depending on cell context, aberrant expression of Notch-1 and Notch-3 can employ either tumor suppressive or oncogenic roles. However, their roles in oral squamous cell carcinoma (OSCC) remain unclear, particularly in Indian population due to lack of availability of data from India. Therefore, we sought to explore the roles of Notch-1 and Notch-3 in OSCC and to investigate their influence on the disease outcome of patients. Materials and Method: Protein expression of Notch-1 and Notch-3 were localized immunohistochemically in 120 pre-therapeutic OSCC patients and assessed for their roles in disease outcomes. Results: Protein expressions of Notch-1 and Notch-3 were detected in 54% and 61% of patients, respectively. Notch-1 was found to be significantly negatively associated with tumor size ( P = 0.009), nodal status ( P = 0.045), and disease stage ( P = 0.003). Contradictorily, the expression of Notch-3 was found to be positively correlated with tumor size ( P = 0.003), nodal status ( P = 0.012), and disease stage ( P = 0.001). In a Cox multivariate analysis, Notch-1 ( P = 0.037) acts as an independent favorable prognosticator for disease-free survival (DFS). For overall survival (OS), Notch-3 ( P = 0.006) remained an unfavorable prognostic parameter for predicting worse OS. Conclusion: Notch-1 and Notch-3 are useful prognosticators; however, Notch-1 acts as a tumor suppressor, whereas, Notch-3 acts as an oncogene correlating with aggressive phenotype. Therefore, it is very important to study both markers for OSCC patients to add prognostic information and thereby help guide therapeutic decisions.