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Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene
Author(s) -
Schumann H.,
Roth W.,
Has C.,
Volz A.,
ErfurtBerge C.,
Magin T.M.,
BrucknerTuderman L.
Publication year - 2012
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2012.11075.x
Subject(s) - epidermolysis bullosa simplex , keratin 5 , keratin 14 , biology , mutation , keratin 8 , keratin , epidermolysis bullosa , palmoplantar keratoderma , pathology , keratinocyte , desmoplakin , dyskeratosis , hyperkeratosis , cancer research , gene , genetics , medicine , cell culture , transgene , genetically modified mouse
Summary Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14  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 KRT5 and KRT14  genes identified the novel KRT 5 mutation p.E477D. 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 p120‐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.

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