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. Cancer 1999;86:2602–11. © 1999 American Cancer Society. Factors in plasminogen activation were assayed in 100 colorectal carcinoma tissues. Higher expression of urokinase plasminogen activator receptor (uPAR) was related to poor prognosis in patients with colorectal carcinoma and the calculated ratios of plasminogen activator type 1 over either uPAR or uPAR‐bound urokinase‐type plasminogen activator correlated positively with tumor size.