Tissue microarray-based analysis shows phospho-β-catenin expression in malignant melanoma is associated with poor outcome
Tissue microarray-based analysis shows phospho-β-catenin expression in malignant melanoma is associated with poor outcome
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DOI：
10.1002/ijc.10893
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发表时间：
2003-02-20
影响因子：
6.4
通讯作者：
Rimm, DL
中科院分区：
文献类型：
--
作者：
Kielhorn, E;Provost, E;Rimm, DL
除了浸润深度外，几乎没有什么预后标志物可以预测黑色素瘤的预后。最近已经显示β-连环蛋白癌基因突变或显示改变的亚细胞定位，表明β-连环蛋白介导的信号传导的激活在肿瘤发生中起作用。我们假设，评估活化β-连环蛋白，检测磷酸特异性抗体，可能是有用的，以预测黑色素瘤的结果。我们使用β-连环蛋白和磷酸-β-连环蛋白的免疫组织化学分析，首先验证磷酸-β-连环蛋白抗体的特异性，然后在基于组织芯片的研究中测定表达。β-连环蛋白的亚细胞定位在某些情况下是膜性的，而在其他情况下是细胞质和细胞核。我们验证了ser 33/37/thr 41磷酸-β-连环蛋白抗体在转染细胞中的特异性，并表明在培养细胞和人体组织中，表达几乎完全定位于细胞核。总的和磷酸化β-连环蛋白抗体的评价表明，细胞质/细胞核染色在原发性病变中更常见，而细胞核磷酸化β-连环蛋白在转移性病变中更常见。高水平的核磷酸化β-连环蛋白与显著更差的总生存率相关（5年总生存率为51% vs. 25%，p = 0.046）。这些结果表明，磷酸化特异性抗体β-连环蛋白定义了一个独特的子集的情况下，监测磷酸化β-连环蛋白的表达可能是有用的恶性黑色素瘤的预后评估。(C)2002 Wiley-Liss，Inc.
Beyond depth of invasion, there are very few prognostic markers to predict outcome in melanoma. It has been shown recently that the beta-catenin oncogene is mutated or shows altered subcellular localization suggesting that activation of beta-catenin mediated signaling plays a role in oncogenesis. We hypothesize that assessment of activated beta-catenin, as detected by a phospho-specific antibody, may be useful to predict outcome in melanoma. We use immuno-histochemical analysis of beta-catenin and phospho-beta-catenin, first to verify the specificity of the phospho-beta-catenin antibody and then to assay expression in a tissue microarray-based study. The subcellular localization of beta-catenin is membranous in some cases and cytoplasmic and nuclear in others. We validate the specificity of a ser33/37/thr41 phospho-beta-catenin antibody in transfected cells and show that the expression is almost exclusively localized to the nucleus in both cultured cells and human tissue. Evaluation of both total and phospho-beta-catenin antibodies showed that cytoplasmic/nuclear staining was more common in primary lesions, whereas nuclear phospho-beta-catenin was more common in metastatic lesions. High levels of nuclear phospho-beta-catenin are associated with significantly worse overall survival (51% vs. 25% overall survival at 5 years, p = 0.046). These results suggest that phosphospecific antibodies to beta-catenin define a unique subset of cases and that monitoring of phospho-beta-catenin expression may be useful for assessing prognosis in malignant melanoma. (C) 2002 Wiley-Liss, Inc.