Prognostic significance of cadherin-based adhesion molecules in cutaneous malignant melanoma
Prognostic significance of cadherin-based adhesion molecules in cutaneous malignant melanoma
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DOI：
10.1158/1055-9965.epi-07-2729
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发表时间：
2008-04-01
影响因子：
3.8
通讯作者：
Rothberg, Bonnie E. Gould
中科院分区：
文献类型：
--
作者：
Kreizenbeck, Gretchen M.;Berger, Aaron J.;Rothberg, Bonnie E. Gould
背景资料：新的分子预后标志物，可以补充验证皮肤恶性黑色素瘤的临床病理学相关的需要是公认的。介导上皮-间充质转化（癌细胞从其母体肿瘤脱离的过程）的蛋白质是重要的候选蛋白。方法：E-cadherin、N-cadherin和P-cadherin（调节细胞间粘附的钙依赖性跨膜糖蛋白）及其衔接子α-连环蛋白、β-连环蛋白和p120-连环蛋白的预后相关性，使用基于荧光的免疫组织化学方法和数字捕获显微照片上的蛋白质表达自动定量分析，对201例原发性和274例转移性黑色素瘤进行了评估。（对数秩= 7.31; P = 0.03），但在调整已建立的临床病理学相关性后没有保持显著性（P = 0.50）。在单变量（P = 0.13）和多变量（P = 0.10）分析中，E-钙粘蛋白水平越高，预后越好。所有六个标志物的复合特征的分层聚类确定了四个独特的聚类，产生了差异的总生存期（对数秩= 10.54; P = 0.01）。表达高E-钙粘蛋白和N-钙粘蛋白水平的簇4具有最有利的结果，并且以低E-钙粘蛋白和α-连环蛋白但中等N-钙粘蛋白为特征的簇2显示最不利的结果。聚类2在多变量分析中仍具有显著性（风险比，3.29; 95%置信区间，1.50-7.19; P = 0.003）。结论：尽管没有一种基于钙粘蛋白的粘附分子是独立的预后因子，但多标记物特征具有显著性。与上皮源性肿瘤相似，E-钙粘蛋白的缺失与不良结局相关。相反，对于神经嵴来源的皮肤恶性黑色素瘤，N-钙粘蛋白过表达可能与成功的上皮-间质转化或良好分化的肿瘤相关。需要额外的钙粘蛋白谱来区分这些独特的表型。
Background: The need for novel molecular prognostic markers that can supplement validated clinicopathologic correlates for cutaneous malignant melanoma is well recognized. Proteins that mediate the epithelial-mesenchymal transition, the process by which a cancer cell disengages from its parent tumor, are important candidates.Methods: The prognostic relevance of E-cadherin, N-cadherin, and P-cadherin, calcium-dependent transmembrane glycoproteins that regulate cell-cell adhesion, and their adaptors, alpha-catenin, beta-catenin, and p120-catenin, was evaluated on a cohort of 201 primary and 274 metastatic melanoma tumors using fluorescence-based immunohistochemical methods and Automated Quantitative Analysis of protein expression on digitally captured photomicrographs.Results: Increasing levels of N-cadherin expression improved overall survival (log-rank = 7.31; P = 0.03) but did not retain significance following adjustment for established clinicopathologic correlates (P = 0.50). Higher levels of E-cadherin approached significance for favorable prognosis on both univariate (P = 0.13) and multivariable (P = 0.10) analyses. Hierarchical clustering of the composite profiles for all six markers identified four unique clusters that yielded differential overall survival (log-rank = 10.54; P = 0.01). Cluster 4, expressing high E-cadherin and N-cadherin levels, possessed the most favorable outcome and cluster 2, featuring low E-cadherin and a-catenin but modest N-cadherin, showed least favorable outcomes. Cluster 2 remained significant on multivariable analysis (hazard ratio, 3.29; 95% confidence interval, 1.50-7.19; P = 0.003).Conclusions: Although none of the cadherin-based adhesion molecules were independently prognostic, multimarker profiles were significant. Similar to epithelial-derived tumors, loss of E-cadherin correlates with poor outcome. In contrast, for neural crest-derived cutaneous malignant melanoma, N-cadherin overexpression can be associated with either a successful epithelial-mesenchymal transition or a favorably differentiated tumor. Additional cadherin profiles are needed to discriminate these distinctive phenotypes.