MUC1 and nuclear β-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis

MUC1 and nuclear β-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis
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DOI:
10.1158/1078-0432.ccr-03-0163
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发表时间:
2004-04-15
影响因子:
11.5
通讯作者:
Dienes, HP
Dienes, HP
中科院分区:
医学1区
文献类型:
--
作者:
Baldus, SE;Mönig, SP;Dienes, HP

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目的:MUC 1的过表达以及粘蛋白与β-连环蛋白的胞浆相互作用被认为参与了结直肠癌的发生。最近发表的体外实验数据表明MUC 1过表达导致核β-连环蛋白稳态水平的增加。我们试图阐明这两种分子在结直肠癌中的共表达,以证明可能与临床,病理和预后data.Experimental设计:免疫组化双染色研究进行了一系列的205例结直肠癌患者的MUC 1和β-连环蛋白的表达和亚细胞分布的特点。结果:MUC 1在肿瘤中心和浸润前沿呈强阳性表达,阳性率为50%。关于β-连环蛋白在侵袭性肿瘤部分的核积累,获得了类似的结果。MUC 1蛋白在肿瘤中心的表达与低分化程度显著相关,在左结肠癌和直肠癌中,肿瘤周围的核β-连环蛋白更常见。在单因素分析中,MUC 1和β-连环蛋白的过表达,以及它们在浸润前沿的核共表达与较差的总生存率相关。然而,只有病理肿瘤淋巴结转移分期和MUC 1在浸润front.Conclusions显示为独立的预后因素:这些结果表明,MUC 1和P-catenin共表达在大肠癌的浸润前沿,这一特点是与加速病程和预后不良。
Purpose: Overexpression of MUC1 and cytosolic interaction of the mucin with beta-catenin are claimed to be involved in colorectal carcinogenesis. lit vitro data published recently suggest that MUC1 overexpression results in an increase of steady state levels of nuclear beta-catenin. We tried to elucidate the coexpression of both molecules in colorectal cancer to demonstrate possible correlations with clinical, pathological, and prognostic data.Experimental Design: An immunohistochemical double staining study was performed to characterize the expression and subcellular distribution of MUC1 and beta-catenin in a series of 205 patients with colorectal carcinoma. The results were correlated with clinicopathological variables as well as overall survival.Results: MUC1 was strongly expressed in the tumor center and at the invasion front in similar to50% of the cases. Similar results were obtained with regard to nuclear accumulation of beta-catenin at the invasive tumor parts. MUC1 protein expression in the tumor center correlated significantly with a low grade of differentiation, and nuclear beta-catenin in the tumor periphery was more frequent in carcinomas of the left colon and rectum. Overexpression of MUC1 and beta-catenin, as well as their nuclear coexpression at the invasion front correlated with a worse overall survival in an univariate analysis. However, only pathological tumor-node-metastasis staging and MUC1 at the invasion front revealed as independent prognostic factors.Conclusions: These results suggest that MUC1 and P-catenin are coexpressed at the invasion front of colorectal carcinomas and that this feature is associated with an accelerated course of disease and worse prognosis.