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

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Abstract
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.
Funding Information
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (305891/2024‐3)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Code 001)

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