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Urokinase-type plasminogen activator (u-PA) is a serine protease that has been implicated in cancer invasion and metastasis. We quantitated u-PA levels in normal colorectal mucosa, adenomatous polyps, and colorectal cancers and correlated these levels with clinicopathological features and patient survival. Detergent extracts were prepared from 133 colorectal cancers, 133 corresponding colorectal mucosal samples, and 15 synchronous adenomatous polyps. u-PA levels were determined using an ELISA, and a cancer:normal u-PA ratio was calculated for each case. u-PA levels were higher in cancers than in normal tissues, whereas adenomas had intermediate levels (P < 0.0001). u-PA levels were unrelated to clinical or pathological features. Survival was decreased in patients with a high cancer:normal u-PA ratio (P = 0.007). Multivariate survival analysis of patients undergoing curative surgery confirmed that the u-PA cancer:normal ratio was related to outcome (relative risk, 2.67; P = 0.02) and was independent of tumor stage (relative risk, 2.26; P = 0.03). Our study suggests that a high ratio of cancer to normal mucosal u-PA indicates an increased risk of colorectal cancer progression. Measurement of u-PA may provide useful prognostic information in patients undergoing curative surgery for colorectal cancer. The aggressive behavior of colorectal cancers with a high u-PA ratio suggests that the protease might be a suitable target for the development of therapeutic agents to prevent invasion and metastasis.

This study determined whether the long-term outcome of patients with obstructing colorectal cancer could be related to conventional pathological prognostic variables or to other clinical, operative or histological features. Ninety-eight patients with bowel obstruction who had undergone potentially curative surgery and survived the postoperative period were studied. Features related to poor long-term outcome after a median follow-up of 5 years included bowel perforation at initial operation (P = 0.007), advanced tumour stage (P < 0.001), poor tumour differentiation (P = 0.02), mucin production by tumour (P = 0.004) and the presence of vascular (P = 0.08) and neural (P = 0.004) invasion. Outcome was not significantly related to the seniority of the operating surgeon (P = 0.52), even when this was adjusted for potentially confounding variables (adjusted hazard rate ratio for trainee surgeons 1.4 (95 per cent confidence interval 0.9-2.4), P = 0.16). Conventional prognostic features may help to identify the majority of patients with obstructed colorectal cancer at high risk of tumour recurrence and death.