Expression of desmosomal proteins in squamous cell carcinomas of the skin

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.