Urokinase-type plasminogen activator (u-PA) antigen is a predictor of early relapse in breast cancer

Jänicke, F.; Hafter, R.; Hollrieder, A.; Babic, Rudolf; Ulm, Kurt; Gössner, W.; Graeff, H.

doi:10.1016/0268-9499(90)90001-z

Cited by 180 publications

(101 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In agreement with all earlier published studies, we found a correlation between uPA and PAI-I (Janicke et al, 1990(Janicke et al, , 1991(Janicke et al, , 1993Bouchet et al, 1994;Foekens et al, 1994a and b).…”

Section: Discussionsupporting

confidence: 94%

“…The picture for PAI-I is more consistent because, in all studies (Janicke et al, 1990(Janicke et al, , 1991Bouchet et al, 1994;Foekens et al, 1994a and b) but one, PAI-I retains its independent prognostic significance for recurrence. The one study, which in the overall population was non-significant (Janicke et al, 1993), showed PAI-1 as an independent prognosticator in a subgroup analysis of the node-negative group.…”

Section: Discussionmentioning

confidence: 74%

See 1 more Smart Citation

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer

Knoop

Andreasen²,

Hansen³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary The uPA-mediated pathway of plasminogen activation is central to cancer metastasis. Whether uPA and PAI-1 are related to local recurrence, metastatic spread or both is not clear. We present a retrospective study of 429 primary breast cancer patients with a median followup of 5.1 years, in which the levels of uPA and PAI-1 in tumour extracts were analysed by means of an enzyme-linked immunosorbent assay.The median values of uPA and PAI-1, which were used as cut-off points, were 4.5 and 11.1 ng mg-1 protein respectively. The levels of uPA and PAI-1 were correlated with tumour size, degree of anaplasia, steroid receptor status and number of positive nodes. Patients with high content of either uPA or PAI-1 had increased risk of relapse and death. We demonstrated an independent ability of PAI-1 to predict distant metastasis (relative risk 1.7, confidence limits 1.22 and 2.46) and that neither uPA nor PAI-1 provided any information regarding local recurrence.Keywords: urokinase; plasminogen; PAI-1; breast neoplasm mortality; prognosis Cancer cells undergo the following steps during metastasis: detachment from the primary tumour; migration; invasion of the blood and lymphatic vessels; adhesion to and penetration of the endothelium, allowing colonization at distant sites (Liotta et al, 1991). Tumour progression and metastasis also involve various processes that may be called cancer cell-directed tissue remodelling. Examples are angiogenesis (Folkman, 1995) and desmoplasia (Dvorak et al, 1995).Extracellular proteolysis has been implicated in cancer metastasis for many years, with the basic idea that release of proteolytic enzymes from a tumour leads to breakdown of basement membranes and extracellular matrix (ECM), thus allowing cancer cell invasion into the surrounding normal tissue. This is true for plasminogen activators and metalloproteinases (Dan0 et al, 1985;Liotta et al, 1991;Mignatti and Rifkin, 1993;Andreasen et al, 1997). There are two types of plasminogen activator, the urokinase-type uPA and the tissue-type tPA. Both are capable of catalysing the formation of the broad spectrum proteinase plasmin from the inactive zymogen plasminogen. There seems to be general agreement that uPA is most important for generation of plasmin in events involving degradation of ECM, while the primary role of tPA is to generate plasmin for thrombolysis. In relation to cancer metastasis, therefore, uPA is of main interest. There are two main types of inhibitors of plasminogen activator, PAI-1 and PAI-2. The urokinase receptor (uPAR) serves to localize plasminogen activation to cell surfaces (Dan0 et al, 1985;Andreasen et al, 1990Andreasen et al, , 1997Mignatti and Rifkin, 1993 Recent studies have shown that the levels of uPA and PAI-I in malignant tumours vary considerably and are related to the prognosis of the patient (Andreasen et al, 1997). Whether uPA and PAI-I are related to local recurrence, metastatic spread or both is not clear. None of the research groups has to our knowledge looked specifically into the levels of...

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 74%

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer

Knoop

Andreasen²,

Hansen³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…In a preliminary report, in 1988, evidence was presented that high uPA enzyme activity in breast carcinoma extracts correlated with a shortened diseasefree interval for the patients [14]. Tw o years later, in 1990, two groups of investigators j Jänicke and co workers and Duffy and coworkers independently reported measurements of uPA antigen content in breast cancer tissues [15,24]. Applying completely different uPA ELISAs, these authors reported that a high level of immunoreactive uPA is significantly correlated with high relapse rate and associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…The action of these proteases is under control of a cascade response which induces activation of proteolytically active urokinase (uPA) from its precursor pro-uPA [11][12][13]. Recent studies have suggested that the uPA level might be a strong biological indicator of prognosis in breast cancer [14,15] and of response to endocrine therapy in recurrent breast cancer [16], There is also broad interest in the relationship of uPA levels with other types of cancer [17][18][19]. Various EOS As for uPA have been established and reported in the literature, and some of these are commercially available.…”

Section: Introductionmentioning

confidence: 99%

Immunoassays (ELISA) of urokinase-type plasminogen activator (uPA): Report of an EORTC/BIOMED-1 Workshop

Benraad

Geurts-Moespot

Grøndahl-Hansen

et al. 1996

European Journal of Cancer

Self Cite

View full text Add to dashboard Cite

“…The present data demonstrate that in multicentre studies the same ELISA kit should be used, and that external quality assurance (QA) is mandatory. Furthermore, it appears from the present study that standardization of the protein assay as a tissular parameter is imperative.Keywords: uPA; PAI-1; enzyme-linked immunosorbent assay; breast cancer; quality assessment; EORTC During the past decade, convincing evidence has accumulated progression and early death (Duffy et al, 1988;Janicke et al, 1990; suggesting that the urokinase-type plasminogen activator (uPA) Foekens et al, 1992, Spyratos et al, 1992Duffy, 1996). plays a key role in the process of metastasis of human breast Likewise, high levels of the uPA inhibitor PAI-1 also correlate cancer and of other solid malignant tumours (Mignatti and Rifkin, with shorter relapse-free and overall survival of the breast cancer…”

mentioning

confidence: 99%

External quality assessment of trans-European multicentre antigen determinations (enzyme-linked immunosorbent assay) of urokinase-type plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) in human breast cancer tissue extracts

Geurts-Moespot²,

et al. 1998

View full text Add to dashboard Cite

Summary High levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in breast cancer tissue extracts have been associated with rapid disease progression. In these studies, different enzyme-linked immunosorbent assay (ELISA) kits have been applied for the quantification, and consequently the ranges of uPA and PAI-1 levels reported differ considerably. Therefore, the Receptor and Biomarker Study Group (RBSG) of the European Organization for Research and Treatment of Cancer (EORTC) and a consortium of the BIOMED-1 project 'Clinical Relevance of Proteases in Tumor Invasion and Metastasis' initiated three collaborative between-laboratory assessment trials aimed at controlling uPA and PAI-1 antigen analyses. For this purpose, two control preparations were produced from different sources: pooled human breast cancer specimens (QC-240893) and human breast cancer xenografts raised in nude mice (QC-1 01094). The lyophilized preparations were stable for prolonged times (at least 3 and 27 months respectively) at 40C. Furthermore, a good parallelism following dilution was found for uPA and PAI-1. The data from QC trial no. 1 clearly indicated that acceptable betweenlaboratory coefficients of variation (CVs) for uPA (<8.2%) and PAI-1 (<16.6%) in QC-240893 could be achieved when the same type of ELISA kit (American Diagnostica) was used. From the second trial, in which ten EORTC laboratories each received five identical lyophilized QC-101094 samples, it appeared that the within-laboratory variations for uPA and PAI-1 determinations obtained by 'experienced' laboratories were lower (<12.9%) than those from non-experienced laboratories (<36.4%). In a third QC trial, five BIOMED-1 laboratories, all of which employed ELISA procedures for uPA and PAI-1, participated in six subsequent quality assessment rounds receiving five samples of QC-101094. Although for each laboratory the within-run CVs for uPA as well as for PAI-1 were low (<7.8%), the between-run CVs were found to be considerably higher (up to 56.2% for uPA and to 27.6% for PAI-1). Consequently, because of the different ELISA formats used, the absolute analyte values measured in the different laboratories varied substantially. The use of 'common external standards' in the different ELISAs resulted in a significant reduction of the between-laboratory CVs from 61.3% to 15.7% (uPA) and from 42.1% to 19.1% (PAI-1). The present data demonstrate that in multicentre studies the same ELISA kit should be used, and that external quality assurance (QA) is mandatory. Furthermore, it appears from the present study that standardization of the protein assay as a tissular parameter is imperative.Keywords: uPA; PAI-1; enzyme-linked immunosorbent assay; breast cancer; quality assessment; EORTC During the past decade, convincing evidence has accumulated progression and early death (Duffy et al, 1988;Janicke et al, 1990; suggesting that the urokinase-type plasminogen activator (uPA) Foekens et al, 1992, Spyratos et al, 1992Duffy, 1996). plays a k...

show abstract

Urokinase-type plasminogen activator (u-PA) antigen is a predictor of early relapse in breast cancer

Cited by 180 publications

References 27 publications

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer

Immunoassays (ELISA) of urokinase-type plasminogen activator (uPA): Report of an EORTC/BIOMED-1 Workshop

External quality assessment of trans-European multicentre antigen determinations (enzyme-linked immunosorbent assay) of urokinase-type plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) in human breast cancer tissue extracts

Contact Info

Product

Resources

About