Larger and more invasive colorectal carcinoma contains larger amounts of plasminogen activator inhibitor type 1 and its relative ratio over urokinase receptor correlates well with tumor size.

BACKGROUND: Considering recent findings that both urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitors (PAIs) are involved in tumor growth through an urokinase-type plasminogen activator (uPA) activity-independent mechanism, the relation between the presence of these factors in tumor tissue and the clinicopathologic variables in colorectal carcinoma was reevaluated.

METHODS: In 100 colorectal carcinoma patients, antigen levels of u-PA, uPAR, and PAI-1 and PAI-2 were assayed in both tumor tissues and their normal counterparts. Plasma levels of soluble uPAR also were determined.

RESULTS: All uPAR, uPA, PAI-1, and PAI-2 antigen levels in tumor tissue were significantly higher than those in normal tissue. Levels of both uPAR and PAI-1 were significantly higher (3.09 +/- 1.37 and 6.63 +/- 7.49, respectively) in large tumors (>/=50 mm in greatest dimension) than those in smaller tumors (< 50 mm) (2.50 +/- 1.07 and 2.72 +/- 2.70, respectively) (P < 0.05). Significant positive correlation coefficients (r) were obtained between tumor size and the calculated ratios of PAI-1/uPAR (r = 0.490; P < 0.0001) and PAI-1/uPA (r = 0. 469; P < 0.0001). In addition to liver metastases (P = 0.004) and lymph node involvement (P = 0.04), high levels of uPAR (P = 0.05) also were found to be of independent prognostic value by multivariate analysis.

CONCLUSIONS: Higher expression of uPAR was related to poor prognosis of patients with colorectal carcinoma and excess amounts of PAI-1 over uPAR or uPAR-bound uPA appeared to play an important role in tumor progression.