Extracellular Matrix Remodeling in Actinic Cheilitis and Lip Squamous Cell Carcinoma: A Cross‐Sectional Study

BACKGROUND: Actinic cheilitis is a precursor to lip squamous cell carcinoma. How ultraviolet-induced stromal degeneration relates to invasion-related extracellular matrix markers remains unclear. This study investigated basophilic degeneration of collagen, solar elastosis, fibronectin, tenascin-C, and podoplanin in both lesions. METHODS: Specimens of actinic cheilitis (n = 28) and lip squamous cell carcinoma (n = 28) were analyzed. Collagen degeneration, elastosis, and the immunoexpression of fibronectin, tenascin-C, and podoplanin were quantified using digital image analysis. Associations were evaluated using mixed-effects models. RESULTS: Collagen degeneration and elastosis areas were significantly greater in actinic cheilitis (p < 0.001). Lip squamous cell carcinoma exhibited higher stromal fibronectin and podoplanin (p < 0.001), whereas epithelial tenascin-C was higher in actinic cheilitis (p < 0.001). Notably, in both lesions, areas with pronounced collagen degeneration and elastosis were inversely associated with the expression of these invasion-related proteins. CONCLUSIONS: Actinic cheilitis features marked actinic stromal degeneration, whereas lip squamous cell carcinoma exhibits tumor-driven extracellular matrix remodeling with increased invasion-related markers. These findings highlight distinct stromal microenvironment profiles associated with pre-neoplastic and neoplastic lip lesions.