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浸润性癌细胞表面的尿激酶型纤溶酶原激活物受体:远端胃腺癌的预后因素。

Urokinase plasminogen activator receptor on invasive cancer cells: a prognostic factor in distal gastric adenocarcinoma.

机构信息

The Finsen Laboratory, Copenhagen University Hospital, Denmark.

出版信息

Int J Cancer. 2012 Aug 15;131(4):E329-36. doi: 10.1002/ijc.26417. Epub 2011 Oct 20.

Abstract

Gastric cancer is the second cancer causing death worldwide. The five-year survival for this malignancy is below 25% and few parameters have shown an impact on the prognosis of the disease. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Using immunohistochemistry, the prognostic significance of uPAR was evaluated in tissue samples from a retrospective series of 95 gastric cancer patients. uPAR was expressed by neoplastic cells, macrophages, myofibroblasts and neutrophils in both intestinal and diffuse subtypes. No association was demonstrated between the expression of uPAR on cancer cells and histological subtype (p = 0.64) or TNM stage (p = 0.75). Univariate analysis revealed a significant association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor for overall survival in gastric cancer (HR = 2.39; 95% CI: 1.22-4.69; p = 0.011). In consequence, scoring of uPAR-positive cancer cells may be a direct measure for the invasive potential of gastric adenocarcinomas.

摘要

胃癌是全球导致死亡的第二大癌症。这种恶性肿瘤的五年生存率低于 25%,并且很少有参数显示对疾病的预后有影响。尿激酶型纤溶酶原激活物受体(uPAR)参与细胞外基质的降解,通过介导细胞表面相关的纤溶酶原激活,其在胃癌细胞上的存在与微转移和预后不良有关。本研究采用免疫组织化学方法,对 95 例胃癌患者的回顾性系列组织样本中 uPAR 的预后意义进行了评估。在肠型和弥漫型两种亚型中,uPAR 在肿瘤细胞、巨噬细胞、肌成纤维细胞和中性粒细胞中均有表达。uPAR 在肿瘤细胞上的表达与组织学亚型(p=0.64)或 TNM 分期(p=0.75)之间无相关性。单因素分析显示,肿瘤细胞在外周浸润区表达 uPAR 与胃癌患者的总生存率之间存在显著相关性(HR=2.16;95%CI:1.13-4.14;p=0.02)。多因素分析表明,肿瘤细胞浸润前沿的 uPAR 免疫反应活性是胃癌总生存率的独立预后因素(HR=2.39;95%CI:1.22-4.69;p=0.011)。因此,uPAR 阳性肿瘤细胞的评分可能是评估胃腺癌侵袭潜能的直接指标。

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