Toll-Like Receptor 4 up-reulation in oral lichen planus and associated OSCC. Preliminary report

Introduction: Oral Lichen planus (OLP) is a chronic, T-cell mediated muco-cutaneous inflammatory disease defined by the WHO as a potential precancerous condition which is characterized by active epithelium and sub-epithelial accumulation of lymphocytes. OSCC is associated to a particular inflammatory microenvironment. Epithelium-specific signals can activate the inflammatory process via TLRs. Nowadays 13 TLRs have been identified including toll like receptor 4 (TLR-4) which has a binding specificity for oral microorganisms. Purpose: Aim of the study is to evaluate the expression of TLR-4 in OLP and OSCC both associated and not associated to OLP. Methods: We retrospectively analyzed 19 cases of LP, 10 cases of OLP associated OSCC, 53 cases of OSCC not related to OLP with surrounding mucosa. Immunohistochemistry has been performed with automated LSAB-HRP technique using specific Ab detecting TLR-4. Immunostained slides were acquired by digital camera and analyzed by ISE TMA Software (Integrated System Engineering, Milan, Italy), and CellSens V1.9® Olympus image analysis software. Results: TLR-4 was moderately expressed in oral mucosa surrounding OSCC (mean: 28,5) and showed a peak of strong up-regulation in OSCC not related to OLP (mean: 70,6). OLP showed elevated expression of TLR-4 in epithelium (mean: 54,8) and a consequent strong up-regulation in related OSCC (mean: 83,5).These differences were statistically significant with a strong evidence of correlation (p < .001). Conclusions: In this study we demonstrated association between TLR-4 up-regulation and OLP associated OSCC. Inflammatory microenvironment surrounding both non-OLP OSCC and OLP-associated OSCC may increase mitogenic signals without effective cytotoxic anticancer activity.