UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN COLORECTAL-CANCER - RELATIONSHIP WITH CLINICOPATHOLOGICAL FEATURES AND PATIENT OUTCOME

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 color ectal cancers and correlated these levels with clinicopathological fea tures 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 a n 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 ade nomas had intermediate levels (P < 0.0001). u-PA levels were unrelated to clinical or pathological features. Survival was decreased in patie nts with a high cancer:normal u-PA ratio (P = 0.007), Multivariate sur vival 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 m ucosal u-PA indicates an increased risk of colorectal cancer progressi on, Measurement of u-PA may provide useful prognostic information in p atients undergoing curative surgery for colorectal cancer, The aggress ive behavior of colorectal cancers with a high u-PA ratio suggests tha t the protease might be a suitable target for the development of thera peutic agents to prevent invasion and metastasis.