Physiological and pathological changes of plasma urokinase-type plasminogen activator, plasminogen activator inhibitor-1, and urokinase-type plasminogen activator receptor levels in healthy females and breast cancer patients

The plasma urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and urokinase-type plasminogen activator receptor (uPAR) levels were measured in healthy volunteers and breast cancer patients. In pre-menopause healthy females, blood was sampled weekly during one menstruation cycle and menstruation phases (follicular, ovulatory, luteal) were determined by FSH/LH levels. uPA, PAI-1, and uPAR levels were at the nadir during ovulatory phase. uPA level was highest at follicular phase while PAI-1 level was highest at luteal phase. In comparison between pre- and post-menopause states, uPA and uPAR levels were higher in post-menopause state while PAI-1 level was higher in pre-menopause state. In breast cancer patients, uPA, PAI-1, and uPAR positive rates were low when we use the menopause-state-unmatched cut-off points. As we adjusted the cut-off points by menopause states, the PAI-1 positivity increased mainly in post-menopause cancer patients. These findings suggest that there is a minor but possible sequential change of these molecules during menstruation cycle which might blur the pathological positivity in pre-menopause cancer patients. The pathological elevation of PAI-1 was well detected in post-menopause cancer patients, but this elevation did not correlate with tumor burden such as number of metastatic sites or metastatic location. In conclusion, adjustment of physiological changes of uPA, PAI-1, and uPAR is required in determining pathological elevation of the plasma levels in cancer patients, especially in females.This revised version was published online in October 2005 with corrections to the Cover Date.