Focal adhesion kinase is overexpressed in thymic epithelial tumors and may serve as an independent prognostic biomarker.

Abstract

Focal adhesion kinase (FAK) has long been considered to be a key regulator of growth factor receptor- and integrin-mediated signals, with pivotal roles in tumor cells through its kinase activity and scaffolding function. Increased FAK expression and activity has been observed in tumors of various origins and is often associated with a poor prognosis. However, there have been no studies on the aberrant expression of FAK in thymic epithelial tumors to date. The aim of the present study was to evaluate FAK expression in thymic epithelial tumors and to explore the prognostic significance of FAK. FAK expression was investigated in 100 formalin-fixed, paraffin-embedded human thymic epithelial tumor (TET) specimens using immunohistochemical analysis with FAK-specific monoclonal antibody 4.47, and the associations between FAK expression and clinicopathological parameters (including sex, age, tumor size, myasthenia gravis, World Health Organization classification and Masaoka-Koga stage) were analyzed. FAK was significantly overexpressed in TETs compared with in normal thymus tissues (P<0.001). Additionally, FAK overexpression was significantly associated with advanced tumor stages (stages III or IV; P<0.001) and highly aggressive TET subtypes (type B2 and B3 thymomas and thymic carcinomas; P<0.001). Furthermore, FAK overexpression was significantly associated with a worse 10-year overall survival, as determined by univariate analysis (P<0.001). Multivariate analysis revealed that FAK overexpression was an independent prognostic factor for patients with TETs (P=0.034). The results of the present study suggest that FAK serves an important role in the tumorigenesis and progression of TETs. Therefore, FAK may serve as a prognostic biomarker and is a potential therapeutic target for the treatment of TETs.