Prognostic Significance of Epithelial to Mesenchymal Transitions-Related Markers in Oral Squamous Cell Carcinoma

Abstract

Objective: We aimed to evaluate the association between the expression of E-cadherin and vimentin with clinicopathological characteristics and 5-year overall survival in oral squamous cell carcinoma (OSCC). Material and methods: A total of 200 surgically resected OSCC patients treated during 2008-2011 were included. The protein expression analysis was performed using immunohistochemical technique on paraffin-embedded microarray tissue slides Immunoreactivity of proteins were classified into two groups using score of intensity multiplied by percentage of positive tumor cells. A combined analysis was performed using both E-cadherin and vimentin expression to determine Epithelial to mesenchymal transition (EMT) status. Kaplan-Meier method and log-rank test were used to compare the differences among survival curves. Cox-regression analysis was used to obtain independent prognostic factors. Results: The median survival time was 48 months. Twenty-eight (14%) tumors showed loss of E-cadherin expression and 172 (86%) showed preserved E-cadherin expression. Vimentin was negative in 113 (56.5%) tumors and positive in 87(43.5%). E-cadherin (P=0.008) and EMT status (P=0.02) were significantly associated with lymph node metastasis. E-cadherin and vimentin were significantly associated with 5-year overall survival with HR 1.94, 95%CI (1.19-3.16) and HR 1.85, 95% CI (1.26-2.7) respectively. EMT status was also significantly associated with 5-year overall survival, the hazard ratio increased with EMT progression. Complete EMT (loss of E-cadherin expression and positive vimentin) status had higher hazard ratio then individual proteins (HR 2.88, 95% CI (1.44-5.79)). Conclusion: Though both E-cadherin and vimentin expression could act as an independent prognostic factor, a combined evaluation of E-cadherin and vimentin expression to evaluate EMT status could provide a stronger indicator of prognosis in OSCC in addition to age, stage and treatment modality in surgically resected oral squamous cell carcinoma.