title: Expression of TWEAK in normal human skin, dermatitis and epidermal neoplasms: association with proliferation and differentiation of keratinocytes.
abstract: 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.
authors.affiliation: Department of Dermatovenerology, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka, Croatia. peternel@medri.hr
authors.forename: Sandra
authors.initials: S
authors.lastname: Peternel
authors.forename: Teo
authors.initials: T
authors.lastname: Manestar-Blažić
authors.forename: Ines
authors.initials: I
authors.lastname: Brajac
authors.forename: Larisa
authors.initials: L
authors.lastname: Prpić-Massari
authors.forename: Marija
authors.initials: M
authors.lastname: Kaštelan
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D000074049:Cytokine TWEAK; D003872:Dermatitis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D048069:Tumor Necrosis Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D000074049:Cytokine TWEAK; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors