The role of N-cadherin and Notch1 expression in the progression of cutaneous melanoma

Epithelial-mesenchymal transition (EMT) has been suggested to have a driving role in the acquisition of a metastatic potential by melanoma cells (1). Important hallmarks of EMT include both E-cadherin downregulation and increased expression of N-cadherin. This switch in distinct classes of adhesion molecules leads melanoma cells to lose contact with adjacent keratinocytes and interact instead with stromal fibroblasts and endothelial cells, thus promoting dermal and vascular melanoma invasion. This allows tumor cells to migrate to distant host tissues and establish metastases (2). A key regulator in the induction of EMT in melanoma is the Notch1 signaling pathway that, when activated, is prompt to upregulate N-cadherin expression. Consequently, melanoma cells gain enhanced survival, proliferation and invasion properties, driving the tumor toward a more aggressive phenotype (3). In the present study, we investigated the expression of N-cadherin by immunohistochemical analysis in tissue samples from primary cutaneous melanomas and lymph node metastases and found a significant association between N-cadherin and Notch1 presence in the same tumor samples. Moreover, we demonstrated that a high expression of N-cadherin and Notch1, both in primary lesions and in lymph node metastases, predicts an adverse clinical outcome in melanoma patients, suggesting N-cadherin and Notch1 co-presence as a predictive factor in early and advanced stage melanomas.