Prognostic relevance of tumour cell-associated uPAR expression in invasive ductal breast carcinoma
Prognostic relevance of tumour cell-associated uPAR expression in invasive ductal breast carcinoma
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DOI：
10.1111/j.1365-2559.2010.03644.x
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发表时间：
2010-09-01
期刊：
影响因子：
6.4
通讯作者：
Luther, Thomas
中科院分区：
文献类型：
--
作者：
Kotzsch, Matthias;Bernt, Katharina;Luther, Thomas
目的：尿激酶型纤溶酶原激活物受体（uPAR）是肿瘤细胞侵袭和转移过程中细胞周围蛋白水解的关键分子。目的是评估uPAR对侵袭性乳腺癌的预后影响，这取决于肿瘤内哪些细胞类型表达uPAR。方法和结果：使用组织微阵列，通过免疫组织化学方法分析了270例侵袭性乳腺导管癌肿瘤组织标本中uPAR的表达。为了评估uPAR免疫表达，我们使用了表位映射的uPAR结构域II特异性单克隆抗体IID 7。肿瘤细胞（uPAR-Tc）和基质细胞中的高uPAR评分值与高肿瘤分级（G3）显著相关，与雌激素受体状态呈负相关。在多变量分析中，高uPAR-Tc值为无病生存期提供了独立的预后信息（风险比1.93，P = 0.007），当调整了与临床相关的临床病理参数时，而基质细胞中uPAR表达与预后无关。此外，升高的uPAR-Tc值被认为是预后指标，在临床相关的亚组浸润性乳腺癌患者的cancer.Conclusions：在浸润性乳腺癌uPAR表达的浸润性癌细胞，但不是在基质细胞，对患者的预后有显着影响，并有助于更积极的肿瘤表型。
Aims:The urokinase-type plasminogen activator receptor (uPAR) is a key molecule for pericellular proteolysis in tumour cell invasion and metastasis. The aim was to evaluate the prognostic impact of uPAR in invasive breast cancer dependent on which cell types within the tumour express uPAR.Methods and results:uPAR expression was analysed by immunohistochemistry in 270 tumour tissue specimens of invasive ductal breast carcinomas using tissue microarrays. For evaluation of uPAR immunoexpression we used the epitope-mapped, uPAR domain II-specific monoclonal antibody IID7. High uPAR score values in both tumour cells (uPAR-Tc) and stromal cells were significantly related to high tumour grade (G3), and inversely correlated with oestrogen receptor status. On multivariate analysis, high uPAR-Tc values contributed independent prognostic information for disease-free survival (hazard ratio 1.93, P = 0.007) when adjusted for prognostically relevant clinicopathological parameters, whereas uPAR expression in stromal cells was not related to prognosis. In addition, elevated uPAR-Tc values were found to be prognostic indicators in clinically relevant subgroups of patients with invasive breast cancer.Conclusions:In invasive breast cancer uPAR expression in invasive carcinoma cells, but not in stromal cells, has a significant impact on patients' prognosis, and contributes to a more aggressive tumour phenotype.