J Cutan Pathol 2011: 38: 780–789 doi: 10.1111/j.1600-0560.2011.01762.x John Wiley & Sons. Printed in Singapore Copyright © 2011 John Wiley & Sons A/S Journal of Cutaneous Pathology Expression of TWEAK in normal human skin, dermatitis and epidermal neoplasms: association with proliferation and differentiation of keratinocytes Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been implicated in the pathogenesis of various inflammatory pathologies and cancer. We aimed to investigate its expression in normal human skin, inflammatory skin diseases and epidermal neoplasms. Methods: Immunohistochemistry for TWEAK was performed in samples of healthy skin, plaque psoriasis, lichen planus, prurigo nodularis, discoid lupus erythematosus, lichen sclerosus, seborrheic keratosis, common warts, actinic keratosis, Bowen’s disease, keratoacanthoma and basal and squamous cell carcinoma. Double immunofluorescence was used to investigate co-localization of TWEAK with cytokeratin-10 and proliferating cell nuclear antigen (PCNA). Results: TWEAK was robustly expressed in the epidermis of healthy skin and decreased in inflammatory conditions, both in the context of epidermal hyperplasia and atrophy. Decreased TWEAK immunoreactivity was regularly observed in common warts, actinic keratosis and Bowen’s disease, particularly in areas of marked proliferation as evidenced by PCNA-positive nuclei. In squamous cell carcinoma, expression of TWEAK ranged from strong to completely absent, and it mostly corresponded with the expression of cytokeratin-10. TWEAK was absent in keratoacanthoma and basal cell carcinoma. Conclusions: TWEAK is a constitutively expressed epidermal protein whose downregulation might be an early indicator of disturbed differentiation or pathologic proliferation of keratinocytes that accompany inflammatory and neoplastic skin diseases. Keywords: discoid lupus erythematosus, lichen planus, psoriasis, skin cancer, tumor necrosis factor-like weak inducer of apoptosis, TWEAK Peternel S, Manestar-Blaˇ zi´ c T, Brajac I, Prpi´ c-Massari L, Kaˇ stelan M. Expression of TWEAK in normal human skin, dermatitis and epidermal neoplasms: association with proliferation and differentiation of keratinocytes. J Cutan Pathol 2011; 38: 780 – 789. © 2011 John Wiley & Sons A/S. Sandra Peternel, Teo Manestar-Blaˇ zi´ c, Ines Brajac, Larisa Prpi ´ c-Massari and Marija Kaˇ stelan Department of Dermatovenerology, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka, Croatia Dr Sandra Peternel, Department of Dermatovenerology, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka, Croatia Tel: +385 51 658283 Fax: +385 51 658590 e-mail: peternel@medri.hr Accepted for publication May 10, 2011 780