Dillon D A, D'Aquila T, Reynolds A B, Fearon E R, Rimm D L
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Am J Pathol. 1998 Jan;152(1):75-82.
Several studies have reported loss or alteration of expression of E-cadherin in breast cancer and more recently changes in levels of expression of the catenins. We used immunofluorescence to examine E-cadherin, alpha-catenin, beta-catenin, and p120ctn (formerly p120CAS) expression in 91 cases of invasive ductal carcinoma. As expected, all four proteins co-localize to the junctional regions of the cells. Although nuclear localization has been described for beta-catenin in colonic polyps, no examples were found in these breast cancer cases. We found that, although alteration is common in the catenins and E-cadherin, complete loss, as exemplified by E-cadherin in lobular carcinoma (where E-cadherin is frequently mutated), is rarely seen. In contrast, the catenin-related protein p120ctn shows an expression pattern that is significantly unrelated to the other catenins (or E-cadherin), including complete loss of expression in approximately 10% of the cases. No statistically significant correlations with traditional prognostic indicators were observed with any of these proteins. We conclude 1) that expression of E-cadherin and alpha- and beta-catenin are generally retained at the membrane although frequently reduced or altered, 2) that complete loss of p120ctn expression is seen in approximately 10% of the cases, and 3) that there is a significant correlation in the expression of E-cadherin and the catenins but no correlation between these molecules and p120ctn, suggesting an absence of coordinate regulation.
多项研究报告了E-钙黏蛋白在乳腺癌中的表达缺失或改变,最近连环蛋白的表达水平也出现了变化。我们采用免疫荧光法检测了91例浸润性导管癌中E-钙黏蛋白、α-连环蛋白、β-连环蛋白和p120ctn(原p120CAS)的表达。正如预期的那样,所有这四种蛋白都共定位于细胞的连接区域。尽管在结肠息肉中已描述β-连环蛋白存在核定位,但在这些乳腺癌病例中未发现此类情况。我们发现,尽管连环蛋白和E-钙黏蛋白的改变很常见,但像小叶癌中的E-钙黏蛋白(E-钙黏蛋白经常发生突变)那样的完全缺失却很少见。相比之下,连环蛋白相关蛋白p120ctn的表达模式与其他连环蛋白(或E-钙黏蛋白)显著无关,包括在约10%的病例中完全缺失表达。未观察到这些蛋白中的任何一种与传统预后指标存在统计学上的显著相关性。我们得出以下结论:1)E-钙黏蛋白、α-连环蛋白和β-连环蛋白的表达通常保留在细胞膜上,尽管经常减少或改变;2)在约10%的病例中可见p120ctn表达完全缺失;3)E-钙黏蛋白和连环蛋白的表达之间存在显著相关性,但这些分子与p120ctn之间无相关性,这表明不存在协同调节。