Cytokeratin and filaggrin expression in nevus comedonicus

Abstract

To elucidate the pathogenesis of abnormal keratinization in nevus comedonicus, we performed an immunohistochemical study using antikeratin and antifilaggrin (filament-aggregating protein) antibodies. There were no significant differences between nevus comedonicus and normal skin in cytokeratin expression. Although filaggrin was only detected in the granular layer in open comedones, filaggrin was detected in both superficial cells and also intermediate cells in closed comedones, suggesting that filaggrin is involved in the formation of closed comedones. The disorder of terminal differentiation related to filaggrin may play a role in the pathogenesis of abnormal keratinization in nevus comedonicus.

Role of FGFR2-signaling in the pathogenesis of acne

“…145 In fact, perifollicular fibrosis has been observed in lesions of nevus comedonicus. 68 Thus, indirect evidence supports the view that the Apert mutation of FGFR2 leads to infundibular overexpression of IL-1α, which appears to be the driving force of comedo formation in nevus comedonicus and Apert syndrome.…”

“…Unilateral acneiform nevus is considered to represent an extensive variant of nevus comedonicus. 68 The patient's general health status and that of his relatives did not show any abnormalities. Sequencing of the FGFR2 gene revealed a C to G mutation in the nevus which was not present in contralateral unaffected skin and in the DNA isolated from EDTA blood.…”

“…35 Increased expression of fillagrin, a marker of terminal differentiation of epidermis, has been detected in both superficial and intermediate cells in closed comedones of nevus comedonicus. 68 Elevated levels of IL-1α-like bioactivity has been detected in the majority of open comedones in acne vulgaris. 12 Keratinocytes synthesize and secrete various cytokines including IL-1.…”

“…Nevus comedonicus has been considered to be an organoid epidermal nevus involving the hair follicle. 68 A focal clonal defect in growth regulation of infundibular keratinocytes has been postulated. 143 FGFR2b is expressed mainly in the suprabasal spinous layer of epidermis and plays a crucial role in controlling epithelial proliferation and differentiation.…”

Update on Epidermal Nevi and Associated Syndromes

“…It has been hypothesized that NC arises from a developmental defect in the mesodermal component of the pilosebaceous unit, wherein the resulting follicular structure is only able to produce soft keratin, which then accumulates [31]. One study found increased filaggrin expression in closed comedones of NC but found no differences in cytokeratin expression between NC and normal skin [36]. Further studies are needed to elucidate the role of keratin and filaggrin in the pathogenesis of NC.…”