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Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma

Kravvas, Georgios; Xie, Boyu; Millar, Michael; Freeman, Alex; Haider, Aiman; Alnajjar, Hussain M; Muneer, Asif; ... Bunker, Christopher Barry; + view all (2025) Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma. JID Innovations , 5 (4) , Article 100372. 10.1016/j.xjidi.2025.100372. Green open access

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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.

Type: Article
Title: Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.xjidi.2025.100372
Publisher version: https://doi.org/10.1016/j.xjidi.2025.100372
Language: English
Additional information: © 2025 The Authors. Published by Elsevier Inc. on behalf of the Society for Investigative Dermatology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Cancer biology, Squamous cell carcinoma, Wnt signaling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/10208910
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