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Background:  Desmosomal proteins are well established markers of epithelial differentiation. Down-regulation of desmosomal proteins has been suggested to be a sign of reduced adhesiveness in metastasizing cells.

Methods:  We examined actinic keratoses, Bowen's disease, and squamous cell carcinoma (SCC) of the skin for the expression of desmosomal proteins using isoform-specific antibodies on paraffin-embedded sections. Evaluation was performed qualitatively in comparison to the epidermis and semiquantitatively using an area-intensity-score.

Results:  We found no qualitative correlation of desmoplakin or plakoglobin expression with risk of metastasis. Plakophilin 1, desmoglein 1, and the desmocollins 1–3 were found to be heterogeneously expressed in all neoplasms without significant correlation to aggressive tumor behavior. Plakophilin 2 was not expressed in any of the neoplasms examined. As most striking finding, desmoglein 2 was up-regulated qualitatively in half of all neoplasms examined and showed a significant higher proportion of positive cells in high-risk SCC than in low-risk SCC.

Conclusions:  Desmosomal proteins are highly regulated in cutaneous SCC. Only desmoglein 2 expression correlates with risk of metastasis. Desmosomes may still be functional in metastasizing tumor cells.