Plasminogenaktivatorinhibitor 1 und Prognose beim Mammakarzinom

The proteolytic enzyme urokinase-type plasminogen activator (uPA) plays an important role in degrading extracellular matrix. This seems to be an important step in cancer invasion and metastasis. uPA antigen levels correlate significantly with disease recurrence and death in breast cancer. To build up tumour stroma in primary tumours as well as in metastases, inhibition of proteolytic activity is necessary. In this study we investigated the correlation of the Plasminogen Activator Inhibitor 1 (PAI-1), which is the specific inhibitor of uPA and which seems to be important for tumour formation, with prognosis in breast cancer. PAI-1 antigen levels were measured in cytosols of 268 primary breast cancers. In 205 cases we correlated the PAI-1 status (cut-off value: 1 ng/mg) with the clinical outcome. Furthermore we investigated PAI-1 antigen levels in 10 benign breast tumours and 33 metastases. PAI-1 levels were significantly higher in primary carcinomas (median value: 0.62 ng/mg, range: 0 to 30.7) than in benign tumours (median value: 0 ng/mg, range: 0 to 0.1) and metastases showed elevated levels (median value: 1.05 ng/mg, range: 0 to 7.8) in comparison to the primary tumours (Kruskal-Wallis test: p < 0.05). We found that the PAI-1 status correlated significantly with early disease recurrence (Mantel-Test p = 0.0069) and overall survival (Mantel-Test p = 0.0121). After a median follow-up of 32 months (range 2-58), 36% of patients with PAI-1 antigen levels > or = 1 ng/mg (n = 72) showed an early relapse and 24% died, whereas only 19% of patients with PAI-1 antigen levels < 1 ng/mg (n = 133) relapsed and 9% died within the study period. A multivariate analysis revealed that in our study population PAI-1 is not an independent prognostic factor. According to our findings PAI-1 seems to be involved in the formation of extracellular matrix in primary carcinomas and metastases and is related to poor prognosis in breast cancer.