E-cadherin/catenin complex in benign and malignant melanocytic lesions

Abstract

E‐cadherin is a calcium‐dependent cell–cell adhesion molecule expressed by melanocytes and responsible for their adhesion to keratinocytes in vitro. In this study, the expression of E‐cadherin and its associated cytoplasmic proteins α‐, β‐, and γ‐catenin was evaluated in melanocytic lesions by immunohistochemistry. E‐cadherin expression was evaluated in 70 malignant melanomas and the catenins in 35 of these specimens. Twenty benign melanocytic naevi were also evaluated for E‐cadherin and catenin expression. In normal epidermis, E‐cadherin/catenin immunostaining was localized at the intercellular borders. In melanomas, a differential loss of E‐cadherin expression was observed. Membranous E‐cadherin staining was absent in dermal nests of melanomas in their radial growth phase and in Clark level II and III lesions, whereas it was present in a high proportion of melanomas in their vertical growth phase, in Clark level IV and V lesions and in metastasizing melanomas. In contrast, superficial compartments of naevi showed membranous E‐cadherin immunoreactivity and junctional naevus cell nests displayed heterogeneous or diffuse cytoplasmic staining. Cytoplasmic α‐ and β‐catenin, but not γ‐catenin staining were detected in all benign and malignant lesions. These findings indicate that qualitative changes in the expression and cellular localization of E‐cadherin and of α‐, β‐, and γ‐catenin occur in melanocytic lesions and may reflect different stages in their progression. Copyright © 1998 John Wiley & Sons, Ltd.

Loss of E-cadherin Expression in Melanoma Cells Involves Up-regulation of the Transcriptional Repressor Snail

“…In malignant melanomas, loss or down-regulation of E-cadherin was first described in vitro (23,46,47) and later substantiated by immunohistochemical studies of tumor specimens (4,5) in vivo. Functional consequences resulting from loss of Ecadherin expression were elicited by Herlyn and co-workers (19 -21).…”

“…Immunohistochemical studies of E-cadherin expression in malignant melanomas demonstrated significant down-regulation of E-cadherin in the tumor tissue compared with benign melanocytes and melanocytic nevi (4,5). Evidence for the functional relevance of this phenomenon was obtained by Herlyn and co-workers (19 -21), who showed that down-regulation of E-cadherin leads to deregulated control of melanocyte proliferation by keratinocytes and in parallel to an invasive growth behavior.…”

Loss of E-cadherin leads to upregulation of NFκB activity in malignant melanoma

“…Owing to its critical function in intercellular adhesion, E-cadherin has also been assumed to act as a tumor suppressor negatively regulating several critical steps of invasion and metastasis. Loss of E-cadherin expression during tumor development was recently observed in a variety of different tumor types including malignant melanomas (Berx et al, 1995(Berx et al, , 1996Tamura et al, 1996a, b;Silye et al, 1998;Sanders et al, 1999;Melki et al, 2000;Poser et al, 2001). Further, we have shown that inhibition of the expression of the transcriptional repressor snail induced re-expression of Ecadherin in Mel Im melanoma cells (Poser et al, 2001).…”

Cellular cohesion as a prognostic factor in malignant melanoma: a retrospective study with up to 12 years follow-up

“…10,20 Conversely, heterogeneous and variable E-cadherin expression has been reported in melanomas not only between samples but within the same tumour as well. [21][22][23][24] We postulate that such a variability of expression might reflect the proportion of dyscohesive cells in their dermal component. We are currently pursuing this hypothesis by studying the spatial expression of E-cadherin (areas of dyscohesion compared to areas of preservation of cohesion) in melanomas with different dyscohesion scores.…”

“…17 This might be an explanation for the fact that the correlation between morphologically assessed cohesion and prognosis in melanomas is stronger than previous attempts to correlate immunohistochemically detected adhesion molecule expression on melanoma cells with prognosis. 21,23 It could, therefore, be argued that morphological evaluation of tumour cell cohesion may be a simple, cost-effective technique to predict the biologic behaviour of melanomas.…”