There is a need for novel and accurate biomarkers based on genetic abnormalities capable of predicting the risk of malignant transformation of epithelial lesions of the oral cavity. Therefore, we investigate the role of cortactin and focal adhesion kinase (FAK) protein expression in oral dysplasias and their potential utility as cancer risk markers. Cortactin and FAK expression were immunohistochemically evaluated in 64 patients with oral epithelial dysplasia. During follow-up, 17 of 64 patients developed an oral squamous cell carcinoma (OSCC). Increased immunoexpression of cortactin and FAK was found in 52 and 27 of 64 oral dysplasias, respectively, and the expression of both proteins increased with the grade of dysplasia. Increased cortactin and FAK expression was also observed in 13 and 15 OSCC, respectively. Overall, cortactin and FAK expression was maintained or further augmented in the oral squamous cell carcinoma compared to the patient-matched preinvasive lesion. Univariate analysis showed that cortactin and FAK expression, as well as histological grading were significantly associated with oral cancer risk. Strong coexpression of both proteins reflected a significantly higher cancer risk than that of weak to moderate expression or than whenever only one of those proteins showed a strong expression. In multivariate analysis, premalignant oral lesions which exhibited a high coexpression of cortactin and FAK showed a significant risk of developing an OSCC (HR=6.298). Our results indicate that strong immunoexpression of cortactin and FAK, and not only one of them, is a predicting factor for increased cancer risk in oral premalignant lesions.

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