Expression of Raf Kinase Inhibitor Protein (RKIP) is a predictor of uveal melanoma metastasis
Expression of Raf Kinase Inhibitor Protein (RKIP) is a predictor of uveal melanoma metastasis
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DOI：
10.14670/hh-29.1325
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发表时间：
2014-10-01
影响因子：
2
通讯作者：
Longo, Antonio
中科院分区：
文献类型：
--
作者：
Caltabiano, Rosario;Puzzo, Lidia;Longo, Antonio
脉络膜内的黑色素细胞产生的黑色素瘤是成人中最常见的原发性眼内肿瘤。它在生物学上与皮肤黑色素瘤不同，因为它有很强的肝转移倾向。Raf激酶抑制蛋白是一种进化上保守的蛋白质，称为磷脂酰乙醇胺结合蛋白。它是Raf-1的相互作用伴侣，也是Raf-1启动的丝裂原活化蛋白激酶级联反应的负调节因子。Raf激酶抑制剂蛋白表达在许多人类癌症中是低的，并且代表不良预后和/或诱导转移的指标。在本研究中，我们检测了Raf激酶抑制蛋白和磷酸化Raf激酶抑制蛋白在原发性葡萄膜黑色素瘤伴和不伴转移中的免疫组化表达水平，并评估其与其他转移高危特征的相关性，以评估Raf激酶抑制蛋白和磷酸化Raf激酶抑制蛋白是否可用于预测转移。Raf激酶抑制剂蛋白在有转移的患者中表达显著降低，而在无转移的患者中则没有。后者更频繁地具有Raf激酶抑制剂蛋白的高表达。磷酸化Raf激酶抑制剂蛋白的表达在有转移和无转移患者之间无显著差异。Raf激酶抑制剂蛋白的表达是一个合适的和容易确定的标志物在原发性肿瘤，可以预测葡萄膜黑色素瘤转移的风险，因此指导监测和治疗策略。
Melanoma arising from melanocytes within the choroid is the most frequent primary intraocular neoplasm in adults. It is biologically distinct from cutaneous melanoma by a very strong propensity to metastasize the liver. Raf kinase inhibitor protein is a member of an evolutionarily conserved group of proteins called phosphatidylethanolamine-binding proteins. It is an interacting partner of Raf-1 and a negative regulator of the mitogen-activated protein kinase cascade initiated by Raf-1. Raf kinase inhibitor protein expression is low in many human cancers and represents an indicator of poor prognosis and/or induction of metastasis. In the present study, we examined the immunohistochemical expression levels of Raf kinase inhibitor protein and phosphorylated Raf kinase inhibitor protein in primary uveal melanoma with and without metastasis, and evaluated their association with other high risk characteristics for metastasis in order to assess whether Raf kinase inhibitor protein and phosphorylated Raf kinase inhibitor protein can be used to predict metastasis. A significant low expression of Raf kinase inhibitor protein was seen in patients with metastasis but not in patients without metastasis. The latter more frequently had a high expression of Raf kinase inhibitor protein. No significant difference was seen in phosphorylated Raf kinase inhibitor protein expression between patients with and without metastasis. Raf kinase inhibitor protein expression is a suitable and easily determinable marker in the primary tumour that could predict the risk of uveal melanoma to metastasize, and hence guide strategies for monitoring and therapy.