β-Catenin Expression and Activation in Conjunctival Melanoma

Emerentienne Larivé; Michael Nicolas; Gürkan Kaya; Nicolo Riggi; Alexandre P Moulin

doi:10.1159/000500682

β-Catenin Expression and Activation in Conjunctival Melanoma

Dermatopathology (Basel). 2019 Jun 26;6(2):50-62. doi: 10.1159/000500682. eCollection 2019 Apr-Jun.

Authors

Emerentienne Larivé¹, Michael Nicolas², Gürkan Kaya³, Nicolo Riggi⁴, Alexandre P Moulin²

Affiliations

¹ Lausanne University, Lausanne, Switzerland.
² Jules-Gonin Eye Hospital, Lausanne University, FAA, Lausanne, Switzerland.
³ Dermatopathology Unit, Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland.
⁴ Experimental Pathology, Lausanne University Pathology Institute, Lausanne, Switzerland.

Abstract

Purpose: To assess the role of the canonical Wnt pathway via activation of β-catenin in tumor progression of conjunctival melanoma.

Methods: β-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 β-catenin expression was found in 16% of the nevi, in 15% of the melanomas, and in 4% of the PAM. Membranous β-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 β-catenin, nor did it increase cell motility in the wound healing assays. Wnt3a stimulation did not induce nuclear localization of β-catenin in any of the cell lines tested.

Conclusions: In conjunctival melanoma, nuclear localization and activation of β-catenin appear to be limited, suggesting that inhibition of ARF6, responsible for β-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 β-catenin localization.

Keywords: Conjunctiva; Eye; Melanogenesis; Melanoma.