Integrin αV is a prognostic marker for cutaneous squamous cell carcinoma relapse

Early cutaneous squamous cell carcinomas (cSCCs) show epithelial differentiation features and good prognosis, whereas advanced cSCCs present mesenchymal traits and are associated with tumor relapse, metastasis, and poor survival. Prognostic biomarkers for cSCC relapse must therefore be found that accurately predict the clinical course of the disease, since established markers are suboptimal. Using mouse models of cSCC progression, we showed that the emergence of epithelial plastic cancer cells with a hybrid epithelial/mesenchymal phenotype promotes tumor progression to a mesenchymal state. These cells can be identified early on by the expression of integrin αV (ITGAV). Analysis of ITGAV expression in a cohort of primary cSCCs from patients provided prognostic information about the risk of relapse beyond current histopathological parameters. Together, our findings provide an opportunity to clinically implement ITGAV by standard immunodetection approaches and thereby improve patient stratification and therapeutic management. Excised mouse WD-SCCs and MD/PD-SCCs were mechanically minced and enzymatically digested overnight at 37ºC with collagenase type I and dispase. Cell suspensions were filtered and depleted of red blood cells and endothelial cells. Then, full epithelial cancer cells expressing EpCAM and alpha 6-integrin (a6-integrin+/CD45-/EpCAM+ cells), were isolated by flow cytometry-sorter from 3 independent WD-SCCs, and EpCAM+ plastic cancer cells were isolated from 3 independent MD/PD-SCCs. RNA extraction of isolated cells and hybridization on Affymetrix microarrays was carried out to compare whole gene profiling of these populations of cancer cells.