Department of Pathology, Ludwig-Maximilians-Universität (LMU), Thalkirchnerstr, 36, 80337, Munich, Germany.
J Transl Med. 2010 Nov 22;8:123. doi: 10.1186/1479-5876-8-123.
Most colorectal carcinomas are driven by an activation of the canonical Wnt signalling pathway, which promotes the expression of multiple target genes mediating proliferation inavasion and invasion. Upon activation of the Wnt signalling pathway its key player β-catenin translocates from the cytoplasm to the nucleus and binds to members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF-1) family namely LEF-1 and TCF4 which are central mediators of transcription. In this study we investigated the expression of β-Catenin, LEF1 and TCF4 in colorectal carcinomas and their prognostic significance.
Immunohistochemical analyses of LEF-1, TCF4 and nuclear β-Catenin were done using a tissue microarray with 214 colorectal cancer specimens. The expression patterns were compared with each other and the results were correlated with clinicopathologic variables and overall survival in univariate and multivariate analysis.
LEF-1 expression was found in 56 (26%) and TCF4 expression in 99 (46%) of colorectal carcinomas and both were heterogeneously distributed throughout the tumours. Comparing LEF-1, TCF4 and β-catenin expression patterns we found no correlation. In univariate analysis, TCF4 expression turned out to be a negative prognostic factor being associated with shorter overall survival (p = 0.020), whereas LEF-1 expression as well as a LEF-1/TCF4 ratio were positive prognostic factors and correlated with longer overall survival (p = 0.015 respectively p = 0.001). In multivariate analysis, LEF-1 and TCF4 expression were confirmed to be independent predictors of longer respectively shorter overall survival, when considered together with tumour stage, gender and age (risk ratio for LEF-1: 2.66; p = 0.027 risk ratio for TCF4: 2.18; p = 0.014).
This study demonstrates different prognostic values of LEF-1 and TCF4 expression in colorectal cancer patients indicating different regulation of these transcription mediators during tumour progression. Moreover both factors may serve as new potential predictive markers in low stage colon cancer cases in advance.
大多数结直肠癌是由经典 Wnt 信号通路的激活所驱动的，该通路促进了介导增殖、侵袭和转移的多个靶基因的表达。Wnt 信号通路激活后，其关键蛋白β-连环蛋白从细胞质转位到细胞核，并与 T 细胞因子 (TCF)/淋巴增强因子 (LEF-1) 家族的成员结合，即 LEF-1 和 TCF4，它们是转录的核心介质。在这项研究中，我们研究了β-连环蛋白、LEF1 和 TCF4 在结直肠癌中的表达及其预后意义。
使用包含 214 例结直肠癌标本的组织微阵列进行 LEF-1、TCF4 和核β-连环蛋白的免疫组织化学分析。比较了它们的表达模式，并将结果与临床病理变量和单变量及多变量分析中的总生存进行了相关性分析。
在 56 例（26%）结直肠癌中发现 LEF-1 表达，在 99 例（46%）结直肠癌中发现 TCF4 表达，两者在肿瘤中均呈异质性分布。比较 LEF-1、TCF4 和β-连环蛋白的表达模式，我们没有发现相关性。在单变量分析中，TCF4 表达是一个负面的预后因素，与总生存时间较短相关（p=0.020），而 LEF-1 表达以及 LEF-1/TCF4 比值是阳性的预后因素，与总生存时间较长相关（p=0.015 分别为 p=0.001）。在多变量分析中，LEF-1 和 TCF4 表达被证实是总生存时间长短的独立预测因素，当与肿瘤分期、性别和年龄一起考虑时（LEF-1 的风险比：2.66；p=0.027 TCF4 的风险比：2.18；p=0.014）。
本研究表明 LEF-1 和 TCF4 表达在结直肠癌患者中有不同的预后价值，表明在肿瘤进展过程中这些转录介质的调节不同。此外，这两个因素都可能成为低分期结肠癌患者的新的潜在预测标志物。
