Shimazui T, Schalken J A, Giroldi L A, Jansen C F, Akaza H, Koiso K, Debruyne F M, Bringuier P P
Urological Research Laboratory, University Hospital Nijmegen, The Netherlands.
Cancer Res. 1996 Sep 15;56(18):4154-8.
Loss of E-cadherin-mediated adhesion is an important step in the progression of many carcinomas. In model systems, it has been shown that cadherin function requires not only proper E-cadherin expression but also its linkage to the cytoskeleton through catenins. Hence, defects in catenins may cause defective E-cadherin function, and catenins as well as E-cadherin might constitute prognostic indicators. Here, we extend our previous study on E-cadherin in bladder cancer (Cancer Res., 53: 3241-3245, 1993). We have evaluated the expression of E-cadherin-associated cytoplasmic molecules (alpha-, beta-, and gamma-catenins and p120cas) to clarify whether or not the pattern of their expression could provide additional prognostic information beyond that from E-cadherin alone. Forty-eight frozen bladder tumor specimens and 9 samples of normal urothelium were studied by immunohistochemistry. A discrepancy between the E-cadherin and catenin expression pattern was seen in 20.8% of cases. Abnormal expression of each molecule is significantly correlated with tumor grade (P < 0.01) and stage (P < 0.01). Reduced expression of all of the molecules correlates with poor survival (P < 0.01 for each variable). Proportional hazard regression analysis showed that beta-catenin, E-cadherin, and alpha-catenin have strong predictive value, whereas plakoglobin and p120cas have a somewhat lower predictive value. Within patients with invasive tumors, those with a normal staining for either E-cadherin, alpha-catenin, or beta-catenin show a trend toward better survival. However, the difference in survival is significant only for E-cadherin (P < 0.05). Thus, beta-catenin, E-cadherin, and alpha-catenin have similar prognostic values. Therefore, from a practical point of view, the expression of any of these proteins can be of prognostic value for patients with bladder cancer.
E-钙黏蛋白介导的黏附丧失是许多癌症进展中的重要一步。在模型系统中，已表明钙黏蛋白功能不仅需要适当的E-钙黏蛋白表达，还需要其通过连环蛋白与细胞骨架相连。因此，连环蛋白缺陷可能导致E-钙黏蛋白功能缺陷，连环蛋白以及E-钙黏蛋白可能构成预后指标。在此，我们扩展了之前对膀胱癌中E-钙黏蛋白的研究（《癌症研究》，53: 3241 - 3245, 1993）。我们评估了E-钙黏蛋白相关的细胞质分子（α-、β-和γ-连环蛋白以及p120cas）的表达，以阐明其表达模式是否能提供超出单独E-钙黏蛋白的额外预后信息。通过免疫组织化学研究了48例冷冻膀胱肿瘤标本和9例正常尿路上皮样本。在20.8%的病例中观察到E-钙黏蛋白和连环蛋白表达模式存在差异。每个分子的异常表达与肿瘤分级（P < 0.01）和分期（P < 0.01）显著相关。所有分子表达降低与生存不良相关（每个变量P < 0.01）。比例风险回归分析表明，β-连环蛋白、E-钙黏蛋白和α-连环蛋白具有很强的预测价值，而桥粒芯蛋白和p120cas的预测价值稍低。在浸润性肿瘤患者中，E-钙黏蛋白、α-连环蛋白或β-连环蛋白染色正常的患者有生存较好的趋势。然而，仅E-钙黏蛋白的生存差异具有统计学意义（P < 0.05）。因此，β-连环蛋白、E-钙黏蛋白和α-连环蛋白具有相似的预后价值。因此，从实际角度来看，这些蛋白质中的任何一种的表达对膀胱癌患者都可能具有预后价值。
