Multiparametric Prognostic Evaluation of Biological Factors in Primary Breast Cancer

Spyratos, Frédérique; Martin, Pierre Marie; Hacène, K.; Romain, Sylvie; Andrieu, Catherine; Ferrero-Poüs, Magali; Deytieux, S; Doussal, V. Le; Tubiana-Hulin, M.; Brunet, M

doi:10.1093/jnci/84.16.1266

Cited by 112 publications

(57 citation statements)

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“…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. These observations were later extended and confirmed in other studies [25][26][27]. The uPA ELISA kits employed differed in the type of antibodies used, in the type o f standards and in the instructions on how the tissue extracts had to be prepared.…”

Section: Discussionsupporting

confidence: 64%

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

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Section: Discussionsupporting

confidence: 64%

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

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“…This contrasts with the majority of the larger published studies, in which this correlation was not found for uPA (Foucre et al, 1991;Janicke et al, 1991Janicke et al, , 1993Foekens et al, 1992;Spyratos et al, 1992;Gr0ndahl-Hansen et al, 1993;Bianchi et al, 1994;Bouchet et al, 1994;Gohring et al, 1995) and only partly for PAI-I (Foucre et al, 1991;Janicke et al, 1991Janicke et al, , 1993Gr0ndahl-Hansen et al, 1993;Foekens et al, 1994a).…”

Section: Discussionmentioning

confidence: 72%

“…Although the patients of Spyratos et al (1992) and Bouchet et al (1994) seem similar, the first study included cathepsin D and not PAI-1, while the second study did the opposite. This is no doubt the main explanation for the different results regarding metastasis-free survival (MFS).…”

Section: Discussionmentioning

confidence: 99%

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

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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...

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“…Urokinase and its inhibitors have been proposed as new prognostic factors in breast cancer (Duffy et al, 1990;Janicke et al, 1990;Foekens et al, 1992;Spyratos et al, 1992;Bouchet et al 1994;Foekens et al, 1995). However, their use for this purpose can only be envisaged once the results obtained with different assay methods have been compared.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of urokinase plasminogen activator in primary breast carcinoma: comparison of two immunoassay methods

Bouchet

Spyratos²,

Hacène³

et al. 1998

Br J Cancer

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Summary Urokinase-type plasminogen activator (uPA) is a potentially important prognostic factor in breast cancer for identifying patients at high risk of recurrence. This retrospective study assessed two enzyme-linked immunosorbent assay (ELISA) methods measuring uPA antigen levels in 499 primary breast cancer cytosols. Both uPA methods were applied to cytosols used routinely for oestrogen (ER) and progesterone (PgR) receptor assays. uPA was determined using a classical ELISA method (Imubind; American Diagnostica) and a novel automatic immunoluminometric assay (Lia; Sangtec Medical). The uPA Imubind method revealed about twice as much uPA antigen (median 0.75 ng mg-1 protein) as the uPA Lia method (median 0.38 ng mg-1 protein). The correlation coefficient between the two methods was acceptable (r = 0.81), but the two techniques are not interchangeable. Univariate analyses confirmed the poor outcome of patients whose tumours contained large amounts of uPA, regardless of the technique used. Multivariate analyses showed that uPA Imubind and uPA Lia values were both strong independent prognostic factors.Keywords: urokinase plasminogen activator; luminometric immunoassay; prognosis; breast cancer Evidence has accumulated that invasion and metastasis by solid tumours require the action of tumour-associated proteases, which promote the dissolution of the surrounding tumour matrix and basement membranes. In several independent studies of a variety of cancer types, i.e. breast (Dano et al, 1985;Duffy et al, 1988), colorectal (Ganesh et al, 1994;Skelly et al, 1995), lung (Oka et al, 1991), ovary (Kuhn et al, 1994), gastric (Nekarda et al, 1994;Cho et al, 1997) and bladder cancer (Hasui et al, 1992), high levels of the serine protease urokinase-type plasminogen activator (uPA) antigen in tumour extracts were associated with rapid disease progression and poor prognosis. In this study of 499 primary breast cancer tumours, we used two different assay methods for uPA antigen, in order to compare an enzyme-linked immunoassay (uPA Imubind; American Diagnostica) with a new automatic immunoluminometric assay (uPA Lia; Sangtec Medical), to assess the relationships between uPA values and clinical and histological factors and to evaluate the prognostic value of the two methods in multivariate analyses. MATERIALS AND METHODS PatientsThe study group consisted of 499 breast cancer patients treated at the Centre Rene Huguenin (CRH) between 1981 and 1989. The median age was 58 years (range 24-84 years). Patients were selected according to the following criteria: (1) primary, unilateral breast tumour; (2) full follow-up at CRH; (3) previously untreated, Correspondence to: C Bouchet without evidence of metastatic disease or any other malignant tumour at the time of diagnosis; (4) surgery as the first treatment; and (5) complete clinical, histological and biological information, especially concerning hormone receptors and antigen levels of uPA measured in cytosols by the two methods. All tumours were graded by a method based on the criteri...

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Multiparametric Prognostic Evaluation of Biological Factors in Primary Breast Cancer

Abstract: Our retrospective analysis has identified protease expression and tumor cell proliferation rate as important biological prognostic factors in breast cancer. Prospective clinical trials should be undertaken to confirm these results.

Cited by 112 publications

References 0 publications

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

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

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

Prognostic value of urokinase plasminogen activator in primary breast carcinoma: comparison of two immunoassay methods

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