title: Cadherin expression pattern in melanocytic tumors more likely depends on the melanocyte environment than on tumor cell progression.
abstract: BACKGROUND
  Adhesion molecules have been assigned an important role in melanocytic tumor progression. By the loss of E-cadherin, melanocytes might escape the control of neighbouring keratinocytes. Although in vitro data support this hypothesis, there are yet no conclusive immunohistochemical results on cadherin expression in melanocytic tumors.
  
  
  OBJECTIVE
  To gain detailed insight in the expression of cadherins and their cytoplasmic binding partners, the catenins, in various types of benign and malignant melanocytic neoplasms.
  
  
  METHODS
  Immunohistochemical analysis of the expression of E-, P-, and N-cadherin and alpha-, beta-, and gamma-catenin in compound and dermal nevi, Spitz nevi, blue nevi, ultraviolet B (UVB)-irradiated nevi, and malignant melanomas of various tumor thickness.
  
  
  RESULTS
  In both nevi and melanomas, E-cadherin expression in melanocytic cells decreased, following a gradient from junctional to deeper dermal localization. The pattern of E-cadherin expression was more heterogeneous in melanomas than in nevi. In some melanomas, E-cadherin was only weakly positive in the epidermal tumor cells. P-cadherin expression was similar to that of E-cadherin. N-cadherin expression in melanocytic lesions was a rare finding, however, a small percentage of melanomas showed expression in some cell nests. Some Spitz nevi exhibited strong N-cadherin immunoreactivity. Most melanocytic cells were alpha- and beta-catenin-positive and gamma-catenin-negative. UVB irradiation did not influence the expression of cadherins and catenins in melanocytic nevi in vivo.
  
  
  CONCLUSIONS
  It is presumed that the gradual loss of E-cadherin expression represents a reaction of melanocytic cells to altered conditions in the dermal environment, e.g. lack of contact to keratinocytes, or new contact with dermal extracellular matrix molecules, respectively. Melanoma cells apparently are less dependent on these environmental factors and, therefore, show a more heterogeneous expression pattern. This might be of importance for the adaptation of the tumor cells to local requirements. However, in view of our results, a causative role of (loss of ) E-cadherin or (gain of ) N-cadherin for melanocytic tumor progression still remains to be proven.
authors.affiliation: Department of Dermatology, Medical University Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. svenkrengel@gmx.net
authors.forename: Sven
authors.initials: S
authors.lastname: Krengel
authors.forename: F
authors.initials: F
authors.lastname: Grotelüschen
authors.forename: S
authors.initials: S
authors.lastname: Bartsch
authors.forename: M
authors.initials: M
authors.lastname: Tronnier
mesh_terms: D015820:Cadherins / Q000378:metabolism* / Q000528:radiation effects; D002452:Cell Count; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D009508:Nevus, Pigmented / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014466:Ultraviolet Rays
chemical_list: D015820:Cadherins