title: Expression of Wnt5a and its downstream effector beta-catenin in uveal melanoma.
abstract: Upregulation of the Wnt5a pathway has been reported in some cutaneous melanomas but its role in uveal melanoma has not been assessed. We thus sought to determine whether activation of the Wnt-signalling pathway occurred in uveal melanoma through upregulation of some of the key downstream effectors, and whether expression of these components was associated with tumour characteristics and clinical outcome. Expression of Wnt5a, MMP7, and beta-catenin was determined in 40 primary uveal melanomas by immunohistochemistry and correlated with patient prognosis. The proportion of cells immunoreactive for Wnt5a, MMP7, and beta-catenin was higher in tumours from patients with shorter survival and this difference was statistically significant for Wnt5a (P<0.01) and beta-catenin (P=0.02). These data show for the first time activation of the Wnt/beta-catenin-signalling pathway in uveal melanoma and suggest that components of this pathway might be useful prognostic markers as well as attractive therapeutic targets to treat this disease.
authors.affiliation: Department of Ophthalmology, Skin Research Lab, Leiden University Medical Centre, Leiden, The Netherlands. w.zuidervaart@lumc.nl
authors.forename: Wieke
authors.initials: W
authors.lastname: Zuidervaart
authors.forename: Sandra
authors.initials: S
authors.lastname: Pavey
authors.forename: Frans A
authors.initials: FA
authors.lastname: van Nieuwpoort
authors.forename: Leisl
authors.initials: L
authors.lastname: Packer
authors.forename: Coby
authors.initials: C
authors.lastname: Out
authors.forename: Willem
authors.initials: W
authors.lastname: Maat
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Jager
authors.forename: Nelleke A
authors.initials: NA
authors.lastname: Gruis
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
mesh_terms: D006801:Humans; D053208:Kaplan-Meier Estimate; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000378:metabolism* / Q000401:mortality; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7