Urokinase plasminogen activator, a strong independent prognostic factor in breast cancer, analysed in steroid receptor cytosols with a luminometric immunoassay

Urokinase plasminogen activator, a strong independent prognostic factor in breast cancer, analysed in steroid receptor cytosols with a luminometric immunoassay
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DOI:
10.1016/0959-8049(95)00652-4
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发表时间:
1996-05-01
影响因子:
8.4
通讯作者:
Killander, D
Killander, D
中科院分区:
医学1区
文献类型:
--
作者:
Ferno, M;Bendahl, PO;Killander, D

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尿激酶纤溶酶原激活物(uPA)参与不同蛋白酶的激活,所述蛋白酶参与细胞外基质的降解,从而增强肿瘤细胞的侵袭能力。uPA在乳腺癌中具有重要的预后意义。我们分析了尿激酶A与一种新的发光免疫测定法(LIA),适用于细胞溶质样本常规用于雌激素受体(ER)和孕酮受体(PgR)的分析。在0.62 ng uPA/mg蛋白的临界值下,33%(230/688)的样本被归类为代表高uPA肿瘤。研究发现,高uPA含量与较短的无复发生存期(中位观察时间:42个月)、ER和PgR阴性、p53表达增加、DNA非二倍体和高S期分数(SPF)相关,但与淋巴结受累或肿瘤大小(小于或等于20 mm vs>20 mm)无关。在未接受全身辅助治疗的患者亚组中,多变量分析显示uPA与淋巴结状态和SPF一起是独立的预后因素。如果这些结果可以重现,uPA可能是一个适合纳入预后指数的因素。版权所有(C)1996 Elsevier Science Ltd
Urokinase plasminogen activator (uPA) is involved in the activation of different proteases which participate in the degradation of extracellular matrix, thereby enhancing the invasive capacity of tumour cells. uPA has been shown to be of prognostic importance in breast cancer. We have analysed uPA with a new luminometric immunoassay (LIA), applicable in cytosol samples routinely used for oestrogen-receptor (ER) and progesterone-receptor (PgR) analyses. At a cut-off value of 0.62 ng uPA/mg protein, 33% (230/688) samples were classified as representing high uPA tumours. High uPA content was found to be associated with shorter recurrence-free survival (median observation time: 42 months), ER and PgR negativity, increased p53 expression, DNA non-diploidy and a high S-phase fraction (SPF), but not with lymph node involvement or tumour size (less than or equal to 20 mm versus >20 mm). In the subgroup of patients not treated with systemic adjuvant therapy, multivariate analysis showed uPA to be an independent prognostic factor together with lymph node status and SPF. If these results can be reproduced, uPA may be a factor suitable for inclusion in a prognostic index. Copyright (C) 1996 Elsevier Science Ltd