Urokinase plasminogen activator as a prognostic marker in different subgroups of patients with breast cancer

Duffy, Michael J.; Reilly, David; McDermott, Enda; O’Higgins, N.; Fennelly, J. J.; Andreasen, Peter A.

doi:10.1002/1097-0142(19941015)74:8<2276::aid-cncr2820740811>3.0.co;2-7

Cited by 144 publications

(137 citation statements)

References 20 publications

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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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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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“…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%

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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“…The clinical and pathophysiological relevance of such qualities that carry the potential for metastasis is as yet unknown. In the fascinating process of metastasis, many researchers have focused on proteases and adhesion molecules (uPA, cathepsin D, integrins, E-cadherin) (Needham et al, 1988;Duffy et al, 1990). The uPA system is one of the most extensively investigated families of proteases that are secreted in tumour tissue.…”

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confidence: 99%

Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer

Solomayer

Diel²,

Wallwiener³

et al. 1997

Br J Cancer

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SummaryPatients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12 -a tumour-associated glycoprotein typically expressed by almost all breast cancer cells -and the anti-uPA antibody HD-UK9. Thirty-five of the 2E1 1-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPApositive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases.

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Urokinase plasminogen activator as a prognostic marker in different subgroups of patients with breast cancer

Cited by 144 publications

References 20 publications

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

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

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

Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer

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