Epiplakin expression in non-melanoma skin cancer: associations with epithelial-mesenchymal transition markers and tumor invasion

Abstract

Background/Objectives: Epiplakin is a member of the plakin family of proteins involved in cytoskeletal organization, yet its role in skin cancers remains poorly understood. This study aimed to evaluate epiplakin expression in cutaneous skin lesions and to investigate its association with epithelial-mesenchymal transition markers and tumor progression. Methods: The authors retrospectively analyzed skin specimens from squamous cell carcinomas, basal cell carcinomas, and benign intradermal nevi collected between 2021 and 2025. Histopathological features were assessed, and immunohistochemical analysis of Epiplakin, Ecadherin, and N-cadherin was performed. Epiplakin expression was quantified and correlated with cadherin levels and Breslow thickness. Plakin family protein-protein interaction networks were analyzed using KEGG pathway and GO functional enrichment. Results: Protein-protein interaction network analysis demonstrated that plakin family members are associated with multiple cancer-related pathways, with a prominent enrichment in regulating cell proliferation. Epiplakin expression was significantly higher in squamous cell carcinomas (389.94 ± 70.56) compared with basal cell carcinomas (70.39 ± 15.32) and intradermal nevi, while basal cell carcinomas showed a significant decrease compared with normal skin (p < 0.05). In non-melanoma skin cancers, epiplakin expression demonstrated a strong positive correlation with E-cadherin (r = 0.565, p < 0.001) and a weak positive correlation with N-cadherin (r = 0.329, p < 0.05). No significant correlation was observed with Breslow thickness (p > 0.05). Study limitations: Retrospective design and the absence of high-grade squamous cell carcinoma cases in the study population.Conclusions: This is the first study to assess epiplakin expression among epithelial cutaneous cancers. Epiplakin appears to be associated with epithelial---mesenchymal transition and early tumor progression, and its differential expression pattern may provide diagnostic utility.