End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.

Introduction: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and despite the improvement in treatment strategy, 5-year survival rates are about 50%. Identification of patients at high risk of recurrence may enable rigorous personalized post-treatment management. In an earlier proteomics study we observed overexpression of End Binding Protein (EB1) in OSCC. In the present study we investigated the diagnostic and prognostic significance of alterations in expression of EB1 in oral cancer.

Methods: In this retrospective study, the expression of EB1 protein was evaluated in 259 OSCCs, 41 dysplasia, 166 hyperplasia and 126 normal tissues using immunohistochemistry and correlated with clinical-pathological parameters and prognosis of OSCC patients over a follow-up period of up to 91months.

Results: Significantly higher expression of cytoplasmic EB1 was observed in hyperplasia [p<0.001, OR=7.2, 95% CI=4.1-12.8], dysplasia (p<0.001, OR=21.8, CI=8.8-50.2) and OSCCs (p<0.001, OR=10.1, CI=5.8-17.4) in comparison with normal mucosa. Univariate analysis revealed cytoplasmic EB1 association with tumor grade, tumor size and recurrence of the disease. Kaplan Meier survival analysis of EB1 expression showed significantly reduced disease free survival (DFS) (p=0.003). Notably, OSCC patients showing cytoplasmic EB1 overexpression demonstrated significantly reduced DFS (p=0.004, HR=2.1).

Conclusion: EB1 overexpression is an early event in oral tumorigenesis and cytoplasmic EB1 accumulation is associated with poor prognosis and tumor recurrence in OSCC patients.