Zuidervaart Wieke, Pavey Sandra, van Nieuwpoort Frans A, Packer Leisl, Out Coby, Maat Willem, Jager Martine J, Gruis Nelleke A, Hayward Nicholas K
Department of Ophthalmology, Skin Research Lab, Leiden University Medical Centre, Leiden, The Netherlands.
Melanoma Res. 2007 Dec;17(6):380-6. doi: 10.1097/CMR.0b013e3282f1d302.
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.
在一些皮肤黑色素瘤中已报道Wnt5a信号通路上调，但其在葡萄膜黑色素瘤中的作用尚未评估。因此，我们试图确定Wnt信号通路的激活是否通过一些关键下游效应器的上调而发生在葡萄膜黑色素瘤中，以及这些成分的表达是否与肿瘤特征和临床结果相关。通过免疫组织化学测定了40例原发性葡萄膜黑色素瘤中Wnt5a、MMP7和β-连环蛋白的表达，并与患者预后相关联。生存时间较短的患者肿瘤中对Wnt5a、MMP7和β-连环蛋白免疫反应的细胞比例较高，Wnt5a（P<0.01）和β-连环蛋白（P=0.02）的这种差异具有统计学意义。这些数据首次显示葡萄膜黑色素瘤中Wnt/β-连环蛋白信号通路的激活，并表明该通路的成分可能是有用的预后标志物以及治疗该疾病的有吸引力的治疗靶点。
