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?
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| 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.
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| Authors | Jung-Yi Lisa Chan, Kuo-Hsien Wang, Chia-Lang Fang, Wei-Yu Chen |
| Journal | PloS one (PLoS One) Vol. 9 Issue 2 Pg. e89467 ( 2014) ISSN: 1932-6203 [Electronic] United States |
| PMID | 24558502 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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