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.
Kurzen
Hjalmar
H
Department of Dermatology, University of Heidelberg, Heidelberg, Germany. hjalmar_kurzen@med.uni-heidelberg.de
Münzing
Ivonne
I
Hartschuh
Wolfgang
W
D001913:Bowen's Disease / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051187:Desmocollins; D051183:Desmoglein 1; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007642:Keratosis / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051191:Plakophilins; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D019998:Racemases and Epimerases; D012878:Skin Neoplasms / Q000378:metabolism*; D051185:gamma Catenin
D003598:Cytoskeletal Proteins; C495297:DSG1 protein, human; C495314:DSG2 protein, human; C495294:DSP protein, human; D051187:Desmocollins; D051183:Desmoglein 1; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D008565:Membrane Proteins; C495335:PKP1 protein, human; C495337:PKP2 protein, human; D051191:Plakophilins; D020033:Protein Isoforms; D011506:Proteins; D051185:gamma Catenin; D019998:Racemases and Epimerases; C436308:NDP-4-keto-6-deoxy-D-glucose 3',5'-epimerase