Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer

Background and Objectives: Certain pathophysiological markers may be helpful in selecting further therapies for patients with resected colorectal cancer (CRC). The aim of this study was to determine whether expression of proteins of the plasminogen activation system (PAS), which are important in tumor spread and growth, can predict outcome of human CRC. Methods: Protein expression of the PAS, including urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plasminogen (Plg), and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2), was determined in the colonic tissue samples of 56 patients with resected primary CRC by quantitative immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Results: Overexpression of uPA (t-test, P < 0.001), uPAR (P < 0.001) and PAI-1 (P = 0.031) was significantly associated with liver metastatic CRC tumors. Higher uPA or uPAR expression level was significantly correlated with overall survival (OS; log-rank, P = 0.001 and P < 0.0001) and cancer-specific survival (CSS; P = 0.001 and P < 0.0001) after the first CRC resection. The predictive value of both uPA and uPAR in liver metastasis, OS and CSS was independent from other parameters (multivariate Cox regression: all P < 0.001). Conclusions: uPA and uPAR may be independent predictors of liver metastasis, patient overall survival and cancer-specific survival after resection of colorectal tumors. (C) 2003 Wiley-Liss, Inc.