Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma
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 path...
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Elsevier
2025-07-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026725000281 |
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| author | Georgios Kravvas Boyu Xie Michael Millar Alex Freeman Aiman Haider Hussain M. Alnajjar Asif Muneer Aamir Ahmed Christopher Barry Bunker |
| author_facet | Georgios Kravvas Boyu Xie Michael Millar Alex Freeman Aiman Haider Hussain M. Alnajjar Asif Muneer Aamir Ahmed Christopher Barry Bunker |
| author_sort | Georgios Kravvas |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5beeb95196c14b6cb877950a6fa717a3 |
| institution | OA Journals |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-5beeb95196c14b6cb877950a6fa717a32025-08-20T02:36:49ZengElsevierJID Innovations2667-02672025-07-015410037210.1016/j.xjidi.2025.100372Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell CarcinomaGeorgios Kravvas0Boyu Xie1Michael Millar2Alex Freeman3Aiman Haider4Hussain M. Alnajjar5Asif Muneer6Aamir Ahmed7Christopher Barry Bunker8Department of Dermatology, University College London Hospitals NHS Foundation Trust, London, United Kingdom; Correspondence: Georgios Kravvas, Department of Dermatology, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, United Kingdom.Cell and Developmental Biology, Division of Biosciences, University College London, London, United KingdomThe Queen’s Medical Research Institute, College of Medicine & Veterinary Medicine, University of Edinburgh, Edinburgh, United KingdomDepartment of Histopathology, University College London Hospitals NHS Foundation Trust, London, United KingdomDepartment of Histopathology, University College London Hospitals NHS Foundation Trust, London, United KingdomDepartment of Urology, University College London Hospitals NHS Foundation Trust, London, United KingdomDepartment of Urology, University College London Hospitals NHS Foundation Trust, London, United KingdomCell and Developmental Biology, Division of Biosciences, University College London, London, United KingdomDepartment of Dermatology, University College London Hospitals NHS Foundation Trust, London, United KingdomIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S2667026725000281Cancer biologySquamous cell carcinomaWnt signaling |
| spellingShingle | Georgios Kravvas Boyu Xie Michael Millar Alex Freeman Aiman Haider Hussain M. Alnajjar Asif Muneer Aamir Ahmed Christopher Barry Bunker Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma JID Innovations Cancer biology Squamous cell carcinoma Wnt signaling |
| title | Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma |
| title_full | Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma |
| title_fullStr | Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma |
| title_full_unstemmed | Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma |
| title_short | Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma |
| title_sort | wnt signaling in male genital lichen sclerosus differentiated penile intraepithelial neoplasia and penile squamous cell carcinoma |
| topic | Cancer biology Squamous cell carcinoma Wnt signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2667026725000281 |
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