?-Catenin Expression and Activation in Conjunctival Melanoma.

ABSTRACT: Purpose:To assess the role of the canonical Wnt pathway via activation of ?-catenin in tumor progression of conjunctival melanoma. Methods:?-Catenin localization was assessed by immunohistochemistry in 43 conjunctival nevi, 48 primary acquired melanoses (PAM; conjunctival melanocytic intraepithelial neoplasia), and 44 conjunctival melanomas. Activation of the canonical or the noncanonical Wnt pathway was tested in vitro in 4 conjunctival melanoma cell lines with stimulation of either Wnt5a or Wnt3a. Wound healing assays were performed with Wnt5a. Results:Nuclear ?-catenin expression was found in 16% of the nevi, in 15% of the melanomas, and in 4% of the PAM. Membranous ?-catenin expression was identified in all the nevi and PAM and in 97.7% of the melanomas. In vitro, Wnt5a stimulation in the 4 conjunctival melanomas and in 1 skin melanoma cell line did not induce nuclear translocation of ?-catenin, nor did it increase cell motility in the wound healing assays. Wnt3a stimulation did not induce nuclear localization of ?-catenin in any of the cell lines tested. Conclusions:In conjunctival melanoma, nuclear localization and activation of ?-catenin appear to be limited, suggesting that inhibition of ARF6, responsible for ?-catenin activation, in subsets of skin melanoma may not represent a treatment option for this tumor. In vitro, Wnt3a or Wnt5a did not induce nuclear ?-catenin localization.

SUBMITTER: Larive E 

PROVIDER: S-EPMC6827456 | biostudies-literature | 2019 Apr-Jun

REPOSITORIES: biostudies-literature