title: Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy?
abstract: Fibrous papules of the face are hamartomas characterized by stellate-shaped stromal cells, multinucleated giant cells, and proliferative blood vessels in the dermis. The pathogenesis of fibrous papules remains unclear. There is a striking microscopic resemblance between fibrous papules and tuberous sclerosis complex (TSC)-associated angiofibromas. A germline mutation of the TSC1 or TSC2 gene, leading to activation of the mammalian target of rapamycin (mTOR) pathway, accounts for the pathogenesis of TSC-associated angiofibromas. Activated mTOR subsequently activates p70 ribosomal protein S6 kinase (p70S6K) and ribosomal protein S6 (S6) by phosphorylation. Rapamycin, a mTOR inhibitor, is effective in treating TSC-associated angiofibromas. The aim of this study was to understand whether the mTOR pathway is activated in fibrous papules. We studied immunoexpressions of phosphorylated (p-) mTOR effectors in fibrous papules, TSC-associated angiofibromas, and normal skin controls. P-mTOR, p-p70S6K and p-S6 were highly expressed in dermal stromal cells and epidermal keratinocytes in fibrous papules and TSC-associated angiofibromas but not in fibroblasts and epidermal keratinocytes of normal skin controls (p<0.001). The results suggest topical rapamycin may be a novel treatment option for fibrous papules.
authors.affiliation: Department of Dermatology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Jung-Yi Lisa
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan ; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kuo-Hsien
authors.initials: KH
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Lang
authors.initials: CL
authors.lastname: Fang
authors.affiliation: Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
mesh_terms: D018322:Angiofibroma / Q000473:pathology; D004789:Enzyme Activation; D005145:Face / Q000473:pathology*; D006222:Hamartoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014402:Tuberous Sclerosis / Q000473:pathology*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases