Da Forno Philip D, Pringle J Howard, Hutchinson Peter, Osborn Joy, Huang Qiang, Potter Linda, Hancox Rachael A, Fletcher Alan, Saldanha Gerald S
Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom.
Clin Cancer Res. 2008 Sep 15;14(18):5825-32. doi: 10.1158/1078-0432.CCR-07-5104.
Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the importance of WNT5A in melanoma progression or outcome. Therefore, this study aimed to assess the protein expression of WNT5A during melanoma progression and its effect on outcome.
Expression of WNT5A was determined in a series of 59 primary melanomas with matched metastases. To provide a benchmark of progression against which to assess WNT5A, expression of p16(ink4a) was analyzed, as this has been previously well documented in melanoma. The effect of WNT5A protein expression on outcome was assessed in 102 melanomas.
Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression (P = 0.013), whereas there was diminishing p16(ink4a) expression (P = 0.006). Nevi showed relatively strong WNT5A expression. Strong cytoplasmic WNT5A was an independent risk factor for reduced metastasis-free and overall survival in multivariate analysis (P = 0.001 and 0.003, respectively).
Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome.
Wnt配体在发育过程中起主要作用，在癌症中也很重要。表达微阵列分析将该家族的一个成员WNT5A与运动性和侵袭性增加的黑色素瘤亚类相关联。目前尚无主要针对WNT5A在黑色素瘤进展或预后中的重要性的临床样本大型研究。因此，本研究旨在评估WNT5A在黑色素瘤进展过程中的蛋白表达及其对预后的影响。
在一系列59例伴有匹配转移灶的原发性黑色素瘤中测定WNT5A的表达。为了提供一个评估WNT5A的进展基准，分析了p16(ink4a)的表达，因为其在黑色素瘤中的情况此前已有充分记录。在102例黑色素瘤中评估WNT5A蛋白表达对预后的影响。
随着黑色素瘤进展，细胞质WNT5A表达呈增加趋势（P = 0.013），而p16(ink4a)表达则逐渐减少（P = 0.006）。痣显示出相对较强的WNT5A表达。在多变量分析中，强细胞质WNT5A是无转移生存期和总生存期降低的独立危险因素（分别为P = 0.001和0.003）。
随着黑色素瘤进展，细胞质WNT5A增加，且强表达与不良预后相关。
