ArticleJID innovations : skin science from molecules to population health2025
Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma.
Article in JID innovations : skin science from molecules to population health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Male genital lichen sclerosus (MGLSc) is a chronic inflammatory disease causing scarring and significant morbidity, and predisposing individuals to differentiated penile intraepithelial neoplasia (dPeIN) and penile squamous cell carcinoma (PeSCC). Penile carcinogenesis follows two pathways: HPV-related and non-HPV-related. While HPV drives undifferentiated PeIN and warty/basaloid PeSCC, MGLSc is implicated in non-HPV-related dPeIN and "usual" PeSCC. Wnt signalling, pivotal in carcinogenesis, remains underexplored in MGLSc and PeIN. Methods: Tissue arrays from 114 archival samples of MGLSc, dPeIN, and PeSCC were analyzed using multi-label fluorescence staining and confocal microscopy for Wnt4, cyclin D1, c-MYC, and MMP7 expression. Results: Wnt signalling proteins were upregulated in PeSCC: cyclin D1 (2.3-fold), Wnt4 (2-fold), c-MYC (2.5-fold), and MMP7 (1.8-fold). Wnt4 expression increased in MGLSc (p=0.02), while dPeIN showed minimal changes. Altered co-localization of Wnt4/MMP7 (p=0.04) was observed in MGLSc and significant co-localization alterations of several protein pairs were also identified in PeSCC. Conclusion: Wnt signalling plays a role in progression from MGLSc to PeSCC through protein dysregulation. Overexpression and altered interactions in PeSCC highlight its potential as a diagnostic, prognostic, and therapeutic target.
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