c-CBL E3 Ubiquitin Ligase Expression Increases Across the Spectrum of Benign and Malignant T-Cell Skin Diseases

Abstract: Prolonged survival of lesional T cells plays a central role in the pathogenesis of T-cell-mediated dermatoses. We have recently shown that the ubiquitin ligase c-CBL is highly expressed in cutaneous T-cell lymphoma (CTCL) and that its knockdown increases activation-induced cell death, a key pathway for T-cell apoptosis. Here, we extend our work on c-CBL expression in malignant T cells to their nonneoplastic counterparts in benign inflammatory dermatoses. Immunohistochemical staining with anti-c-CBL antibody was performed on lesional biopsies from a total of 65 patients with atopic dermatitis, allergic contact dermatitis, pityriasis rosea, psoriasis vulgaris, lichen planus, mycosis fungoides (MF)/Sézary syndrome (SS) as well as on tonsil tissue from 5 individuals and on 5 human CTCL cell lines. Protein levels were measured in situ using multispectral image analysis, a quantitative method that is ×5 more sensitive than standard immunohistology for antigen detection. There was a significant (P

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