Prognostic value of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in breast carcinomas.
Prognostic value of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in breast carcinomas.
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DOI：
10.1038/bjc.1994.74
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发表时间：
1994-02
影响因子：
8.8
通讯作者：
Oglobine, J
中科院分区：
文献类型：
--
作者：
Bouchet, C;Spyratos, F;Martin, P M;Hacene, K;Gentile, A;Oglobine, J
现在已经明确，蛋白水解酶，包括纤溶酶原激活剂（uPA），在分解细胞外基质中发挥着重要作用，这被认为是转移形成的一个步骤。纤溶酶原激活剂在不同水平上受到控制。已鉴定出两种抑制剂：PAI-1 和 PAI-2，后者对 uPA 更具特异性。在试图确定它们的预后价值时，有必要研究这些参数的相对重要性及其相互作用。我们使用免疫酶法测定 314 个原发性乳腺肿瘤制备的胞质溶胶中的 uPA、PAI-1 和 PAI-2 抗原。对患者进行了至少 6 年的随访，并记录了所有相关的临床和实验室检查结果。单变量分析证实，肿瘤中含有大量 uPA 和 PAI-1 的患者预后较差。此外，低水平的 PAI-2 与总体人群 (P = 0.02)、绝经后妇女 (P = 0.02) 和无淋巴结受累的妇女 (P = 0.02) 的无病生存期较短相关。 “主效应”Cox 模型中的多变量分析将淋巴结受累、宏观肿瘤大小和 PAI-2 确定为重要变量。 “交互”模型考虑到 uPA 及其两种抑制剂之间的相互作用，确定了第一个预后非常差的亚组，即总体人群中高水平的 PAI-1 与低水平的 PAI-2 以及绝经期妇女组中没有淋巴结受累的女性或高水平的 uPA 与低水平的 PAI-2 相关。我们得出结论，PAI-1 提供与 uPA 相同的预后信息，并且似乎不发挥抑制剂的作用。相比之下，PAI-2 增加了 uPA 的预后价值，特别是在绝经后女性中，而 PAI-1 则增加了无淋巴结受累患者的预后价值。
It is now clearly established that proteolytic enzymes, including plasminogen activator (uPA), play an important role in breaking down the extracellular matrix, which is considered to be a step in metastasis formation. Plasminogen activators are controlled at various levels. Two inhibitors, PAI-1 and PAI-2, have been identified, the latter being more specific for uPA. In attempts to determine their prognostic value, it is essential to investigate the relative importance of these parameters and their interactions. We used an immunoenzymatic method to assay uPA, PAI-1 and PAI-2 antigens in cytosols prepared from 314 primary breast tumours. The patients were followed up for a minimum of 6 years and all relevant clinical and laboratory findings were recorded. Univariate analysis confirmed the poor outcome of patients whose tumours contained large amounts of uPA and PAI-1. In addition, low levels of PAI-2 correlated with shorter disease-free survival in the overall population (P = 0.02), post-menopausal women (P = 0.02) and women without lymph node involvement (P = 0.02). Multivariate analysis in the 'main effects' Cox model identified node involvement, macroscopic tumour size and PAI-2 as significant variables. The 'interactive' model, taking into account interactions between uPA and its two inhibitors, identified a first subgroup with a very poor prognosis associating either high levels of PAI-1 with low levels of PAI-2 in the overall population and the women with no node involvement or high levels of uPA with low levels of PAI-2 in the group of menopausal women. We conclude that PAI-1 provides the same prognostic information as uPA, and does not appear to play a role as an inhibitor. In contrast, PAI-2 increases the prognostic value of uPA, particularly in post-menopausal women, and PAI-1 in patients with no node involvement.