Pooled Analysis of Prognostic Impact of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in 8377 Breast Cancer Patients

Look, Maxime P.; Putten, Wim L.J. van; Duffy, Michael J.; Harbeck, Nadia; Christensen, Ib Jarle; Thomssen, Christoph; Kates, Ronald; Spyratos, Frédérique; Fernö, Mårten; Eppenberger‐Castori, Serenella; Sweep, Fred C.G.J.; Ulm, Kurt; Peyrat, Jean‐Philippe; Martin, Pièrre‐Marie; Magdelénat, H.; Brünner, Nils; Duggan, Catherine; Lisboa, B. P.; Bendahl, Pär‐Ola; Quillien, Véronique; Daver, A; Ricolleau, G.; Gelder, Marion E. Meijer–van; Manders, Peggy; Fiets, W. Edward; Blankenstein, Marinus A.; Broët, Philippe; Romain, Sylvie; Daxenbichler, Günter; Windbichler, Gudrun; Čufer, Tanja; Borštnar, Simona; Kueng, Willy; Beex, L.V.A.M.; Klijn, Jan G.M.; O’Higgins, N.; Eppenberger, Urs; Jänicke, F.; Schmitt, Manfred; Foekens, John A.

doi:10.1093/jnci/94.2.116

Cited by 532 publications

(326 citation statements)

References 32 publications

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“…Some previously identified markers do have prognostic value in nodepositive breast cancer, however, since they do not identify a substantial group of patients with an excellent disease outcome, the clinical relevance as prognostic marker for this node-positive patients' group seems to be limited [13,17,18]. The only other signature that could identify a low risk group with a sufficiently good outcome within node-positive patients was the wound signature [9].…”

Section: Discussionmentioning

confidence: 99%

The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study

Mook

Schmidt

Viale

et al. 2008

Breast Cancer Res Treat

261

152

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Section: Discussionmentioning

confidence: 99%

The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study

Mook

Schmidt

Viale

et al. 2008

Breast Cancer Res Treat

261

152

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“…Indeed, PAI-1 is a major inhibitor of u-PA, even when associated to cell surface. However, high expression of PAI-1 is paradoxically associated with marked tumour spreading and poor prognosis (Pappot et al, 1995;Andreasen et al, 1997;Schmitt et al, 1997;Look et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness

Blot

Chen

Vasse³

et al. 2003

Br J Cancer

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In breast cancers, clinical symptoms of inflammation localised around the tumour at the time of diagnosis have been considered to have poor prognosis significance. In this study, the biological mechanisms responsible for the deleterious action of monocytes in cancer were investigated. The incubation of the breast-cancer-derived MDA-MB231 cells with monocytes resulted in an increase in factors involved in cell invasion (i.e. both cancer cells and monocytes-associated urokinase and Tissue Factor, and PAI-1 and MMP-9 secretion). Moreover, the functions of monocytes were also modified. Incubation of monocytes with MDA-MB231 cancer cells resulted in a downregulation in the secretion of the antiproliferative cytokine Oncostatin M, while the apoptotic factor TNF alpha was dramatically increased. However, MDA-MB231 cancer cells have been shown to be resistant towards the apoptotic action of TNF alpha. These findings demonstrate that incubation of MDA-MB231 cancer cells with monocytes induced a crosstalk, which resulted in an increased expression of factors involved in cancer cell invasiveness and in a modification of monocytes function against cancer cells, while inflammatory effects were increased. British Journal of Cancer (2003) The importance of stroma in cancer formation, growth and dissemination is now well established. In order to generate an invasive tumour, cancer cells need several mutations, but also formally necessitate sustenance from noncancer stroma cells, which supply and permit cancer cell growth and invasion. The presence of cytokines and inflammatory cells in cancer stroma, indicating defence reaction against cancer, generally correspond to a poor prognosis (Kleer et al, 2000). Furthermore, in breast cancer, initial presentation with clinical symptoms of inflammation indicates a particular aggressiveness and a worst prognosis than other breast cancers (Chevallier, 1993;Palangie et al, 1994;Kleer et al, 2000). However, the mechanisms leading to the pathological action of stroma-localised inflammatory cells in cancer, such as monocytes, remain poorly understood.The current study was undertaken to explore whether the factors of aggressiveness expressed by cancer cells were modified in the presence of monocytes. We also analysed the consequences of the incubation of monocytes with MDA-MB231 cancer cells on functions of monocytes both in the defence against tumour cells and in inflammatory functions. For this purpose, we tested the consequences of the interaction of the highly invasive breastderived MDA-MB231 cancer cells with monocytes with an in vitro system. MATERIAL AND METHODS Monocytes isolationA measure of 80 mm of blood from healthy volunteers was collected in sterile polypropylene tubes (Costar, Cambridge, MA, USA) containing 7.5 ml of ACD (38 mM citric acid, 74 mM citrate and 136 mM glucose). Platelet-rich plasma was removed by centrifugation (10 min, 100 g at room temperature). Mononuclear cells were collected after centrifugation (45 min, 400 g at room temperature) in Leucosep tubes (Costar, C...

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“…A clinical usefulness of these systems to predict the outcome in breast cancer patients has been expected. Numerous studies have established a prognostic value of the levels of uPA and PAI-1 and of angiogenesis in breast cancer patients (Fox, 1997;Harbeck et al, 1998;Duffy et al, 1999;Look and Foekens, 1999;Look et al, 2002). However, none of these factors are yet used in current clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the level of PAI-1 in primary tumours is one of the most informative biochemical prognostic markers in several cancer types (Duffy, 1996;Harbeck et al, 1998;Knoop et al, 1998;Duffy et al, 1999;Look and Foekens, 1999;Janicke et al, 2001;Look et al, 2002).…”

mentioning

confidence: 99%

Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients

et al. 2003

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Tumour angiogenesis and the levels of plasminogen activator inhibitor type 1 (PAI-1) are both informative prognostic markers in breast cancer. In cell cultures and in animal model systems, PAI-1 has a proangiogenic effect. To evaluate the interrelationship of angiogenesis and the PAI-1 level in breast cancer, we have evaluated the prognostic value of those factors in a total of 228 patients with primary, unilateral, invasive breast cancer, evaluated at a median follow-up time of 12 years. Microvessels were immunohistochemically stained by antibodies against CD34 and quantitated by the Chalkley counting technique. The levels of PAI-1 and its target proteinase uPA in tumour extracts were analysed by ELISA. The Chalkley count was not correlated with the levels of uPA or PAI-1. High values of uPA, PAI-1, and Chalkley count were all significantly correlated with a shorter recurrence-free survival and overall survival. In the multivariate analysis, the uPA level did not show independent prognostic impact for any of the analysed end points. In contrast, the risk of recurrence was independently and significantly predicted by both the PAI-1 level and the Chalkley count, with a hazard ratio (95% CI) of 1.6 (1.01-2.69) and 1.4 (1.02-1.81), respectively. For overall survival, the Chalkley count, but not PAI-1, was of significant independent prognostic value. The risk of death was 1.7 (1.30-2.15) for Chalkley counts in the upper tertile compared to the lower one. We conclude that the PAI-1 level and the Chalkley count are independent prognostic markers for recurrence-free survival in patients with primary breast cancer, suggesting that the prognostic impact of PAI-1 is not only based on its involvement in angiogenesis.

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Pooled Analysis of Prognostic Impact of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in 8377 Breast Cancer Patients

Cited by 532 publications

References 32 publications

The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study

The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1–3 positive lymph nodes in an independent validation study

Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness

Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients

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