Additional research is needed to further establish possible etiological risk factors and to clarify the involvement of PIK3CA and FGFR3 genes in the pathogenesis of seborrheic keratosis of the outer ear canal.
However, mutational analysis from each tumor indicates that the overlapping SK and SCC evolved independently and supports our conclusion that FGFR3 activation is insufficient to drive SCC.
Because FGFR3 and PIK3CA mutations have been reported to be involved in the pathogenesis of seborrhoeic keratosis, we analysed whether these mutations are also present in STK and DPN.
In contrast, the tyrosine kinase receptor FGF receptor-3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs.
The activation of FGFR3 might be a common feature in the tumorigenesis in seborrhoeic keratosis, although the activation does not induce a typical oncogenic signal in keratinocytes.
Somatic oncogenic activating mutations in FGFR3 and/or PIK3CA have recently been described in benign epithelial cutaneous lesions that never progress to malignancy (seborrheic keratoses and epidermal nevi).
Therefore, we examined exons 9 and 20 of PIK3CA and FGFR3 hotspot mutations in EN (n = 33) and SK (n = 62), two proliferative skin lesions lacking malignant potential.
FGFR3 mutations appear to be common genetic alterations in multiple SK with a varying interindividual mutation frequency but without specific intraindividual hot spots.
Based on the occurrence of fibroblast growth factor receptor 3 (FGFR3) mutations in seborrheic keratosis and urothelial carcinomas (UC), and the identification of two young patients with EN and UC, we hypothesized that mutations might occur in EN.
FGFR3 mutations appear to be common genetic alterations in multiple SK with a varying interindividual mutation frequency but without specific intraindividual hot spots.
Recently, the same FGFR3 mutations known from skeletal dysplasia syndromes and urothelial carcinoma have been shown to cause benign human skin tumors such as seborrheic keratoses and epidermal nevi.