PLASMINOGEN-ACTIVATOR INHIBITOR-1 AND PRO GNOSIS IN CARCINOMA OF THE BREAST

The proteolytic enzyme urokinase-type plasminogen activator (uPA) play s an important role in degrading extracellular matrix. This seems to b e an important step in cancer invasion and metastasis. uPA antigen lev els correlate significantly with disease recurrence and death in breas t cancer. To build up tumour stroma ic primary tumours as well as in m etastases, inhibition of proteolytic activity is necessary. In this st udy we investigated the correlation of the Plasminogen Activator Inhib itor 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 le vels 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 va lue: 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 corre lated significantly with early disease recurrence (Mantel-Test p = 0.0 069) and overall survival (Mantel-Test p = 0.0121). After a median fol low up of 32 months (range 2-58), 36% of patients with PAI-1 antigen l evels greater than or equal to 1 ng/mg (n = 72) showed an early relaps e 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 m ultivariate analysis revealed that in our study population PAI-1 is no t an independent prognostic factor. According to our findings PAI-1 se ems to be involved in the formation of extracellular matrix in primary carcinomas and metastases and is related to poor prognosis in breast cancer.