Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene.

[epidermolysis bullosa simplex]

Epidermolysis bullosa simplex (EBS ) is mainly caused by mutations in the KRT 5 and KRT 14 genes . Squamous cell carcinoma (SCC ) represents the second most frequent skin neoplasia with complex aetiology . The molecular events disrupting the orchestrated interplay between the cytoskeleton , cell adhesion molecules and signalling proteins are ill understood in SCC . We describe the molecular background and the unusual course of the disease in a patient with EBS Dowling-Meara , severe keratoderma and a massive verrucous carcinoma . Skin and tumour samples from the patient were analysed using light microscopy , immunohistochemistry and immunofluorescence mapping . Mutation analysis of the KRT 5 and KRT 14 genes identified the novel KRT 5 mutation p .E 477 D . Invasive tumour areas were characterized by downregulation of keratins 5 and 14 , reduced and irregular desmocollin-2 expression and increased expression of keratins 6 , 16 and 17 . Levels of Ki-67 were increased and levels of E -cadherin strongly reduced in the tumour tissue . In this case a novel KRT 5 mutation led to increased fragility of keratinocytes . Desmosome and adherens junctions were destabilized , which may trigger keratinocyte-mediated inflammation , possibly via p 120 -catenin-dependent signalling , suggesting a link between a keratin mutation and SCC , which adds weight to the hypothesis that disturbance of the cytoskeleton represents a major cause in the appearance of the malignant phenotype . Some individuals with EBS may be at risk of developing secondary SCC .