Epithelial-Mesenchymal Expression Phenotype of Primary Melanoma and Matched Metastases and Relationship with Overall Survival

Abstract

E-Cadherin and N-cadherin are important components of epithelial-mesenchymal transition (EMT). The majority of studies on EMT in melanoma have been performed with cultured cell lines or pooled melanoma samples. The goal of our study was to evaluate the expression of E-cadherin and N-cadherin in matched tissue samples from primary and metastatic sites of melanoma and to determine the correlation with survival outcome. We analyzed tissues from 42 melanoma primary lesions and their corresponding metastases, as well as 53 benign nevi, for expression levels of E-cadherin and N-cadherin using immunohistochemical methods. There were heterogenous expression patterns of E- and N-cadherin in both primary and metastatic melanomas. Overall, metastatic tumor showed a decrease in E-cadherin expression and an increase in N-cadherin expression compared to the primary tumor, although the difference did not reach statistical significance (p=0.24 and 0.28 respectively). A switch of membranous expression from E-cadherin to N-cadherin from primary to metastatic melanoma was seen in eight patients (19%). Aberrant E-cadherin expression (defined as negative to weak membranous E-cadherin or positive nuclear E-cadherin expression) was more frequently observed in metastatic than in primary melanomas (p=0.03). Multivariate analysis showed that absence of N-cadherin expression in primary melanomas and the presence of aberrant E-cadherin expression in primary melanomas and metastatic melanomas was associated with a significantly worse overall survival. Our data support the importance of E-cadherin and N-cadherin proteins in melanoma progression and patient survival.

Keywords: E-cadherin; Epithelial–mesenchymal transition; N-cadherin; melanoma; metastasis.