Impact of E-Cadherin Expression Pattern in Melanocytic Nevi and Cutaneous Malignant Melanoma
To explore the relationship between the immunohistochemical expression of E-cadherin and the relevant clinicopathologic features in various types of melanocytic nevi and cutaneous malignant melanoma (CMM). Using standard immunohistochemical techniques, we examined 30 CMMs, 30 melanocytic nevi and 10 sex- and age-matched volunteers for the expression of E-cadherin. A total of 90% of melanocytic nevi and all dysplastic nevi showed positive cytoplasmic immunoreactivity for E-cadherin with decreased intensity at the deeply located cells. A significant difference was noticed between types of CMM regarding the pattern of immunostaining of E-cadherin (p < 0.01), whereas all nodular malignant melanomas (NMMs) express the membranous pattern in contrast to the cytoplasmic one in other types of CMM. Reduced overall survival was significantly associated with advanced stage, late Clark level and membranous pattern of E-cadherin expression. E-cadherin expression in nevi is related to the degree of melanocytic maturation. Qualitative changes in the expression and cellular localization of E-cadherin are observed in melanoma that may reflect different stages of progression with molecular changes and may imply a prognostic marker.
- [Show abstract] [Hide abstract] ABSTRACT: Cutaneous melanoma is associated with strong prognostic phenotypic features such as gender, Breslow's thickness, and ulceration although the biological significance of these variables is largely unknown. It is likely that these features are surrogates of important biological events rather than promoting directly melanoma progression. High-throughput expression studies have helped deciphering the mechanism and role of melanoma cells replication. Another important phenotypic variable in melanoma is the presence of histopathological features of chronic sun exposure damage. The presence or absence of solar elastosis correlates with the rate and the type of BRAF mutations. Genetic defects found in cutaneous melanoma involve most often receptor tyrosine kinase and downstream kinase pathways. Thus, the mitogen-activated protein kinase pathway and the PI3K pathway are activated in most melanomas. BRAF has a recurrent gain-of-function mutation V600E in about 7 % of all cancers and 43-50 % of melanomas. Anti-BRAF therapy has been the first targeted therapy of metastatic melanomas and completely changed the therapeutic landscape. One of the most important unmet needs in the melanoma field is to shift from prognostication based on artificial segmentation of continuous variables to continuous likelihood scores for diagnosis, prognosis, and response to treatment predictions. This implies to use shared biomarkers and clinical databases. © 2014 Springer Science+Business Media New York. All rights are reserved.0Comments 0Citations