A20 as a Potential New Tool in Predicting Recurrence and Patient's Survival in Oral Squamous Cell Carcinoma

A20, known as a potent inhibitor of NF-kappa B signaling, has been characterized in numerous clinical as well as preclinical studies. Recently, especially in various malignant diseases, the prognostic and therapeutic relevance of A20 was investigated. In oral squamous cell carcinoma (OSCC) however, the characterization of A20 is uncharted territory. We analyzed a tissue microarray (TMA) of 229 surgically-treated OSCC patients (2003-2013). Immunohistochemical (IHC) stainings were performed for A20 and CD3; additionally, standard haematoxylin-eosin staining was applied. IHC findings were correlated with a comprehensive dataset, comprising clinical and pathohistological information. A20 expression was analyzed in tumor cells as well as in tumor infiltrating lymphocytes (TILs) and correlated with the overall survival (OS) and recurrence-free survival (RFS) using uni- and multivariable Cox regression. The median follow-up time was 10.9 years and the A20 expression was significantly decreased in CD3+ TILs compared to mucosa-infiltrating lymphocytes (MILs). In the Kaplan-Meier analyses, higher A20 expression in TILs was correlated with better OS (p = 0.017) and RFS (p = 0.020). In the multivariable survival analysis, A20 overexpression correlated with improved OS (HR: 0.582; 95% CI 0.388-0.873, p = 0.009) and RFS (HR 0.605; 95% CI 0.411-0.889, p = 0.011). Our results indicate a novel prognostic role for A20 in OSCC. Due to its elevated expression in TILs, further research is highly desirable, which therefore could offer new therapeutic opportunities for patients suffering from OSCC.

Automated summary

A20 has been identified as a potent inhibitor of NF-kappa B signaling in numerous clinical and preclinical studies. Its prognostic and therapeutic relevance has been investigated in various malignant diseases, but its characterization in oral squamous cell carcinoma (OSCC) is unknown. In this study, the expression of A20 in OSCC patients was examined using immunohistochemical staining. Higher expression of A20 in tumor infiltrating lymphocytes (TILs) was found to be associated with better overall survival (OS) and recurrence-free survival (RFS). These findings suggest a novel prognostic role for A20 in OSCC and highlight the potential for new therapeutic opportunities.