PROGNOSTIC RELEVANCE OF PLASMINOGEN ACTIVATORS AND THEIR INHIBITORS IN COLORECTAL-CANCER

Human colorectal carcinogenesis has been shown previously to be associ ated with impressive changes in the tissue levels of plasminogen activ ators and their inhibitors, exemplified by an increase in the urokinas e-type plasminogen activator (u-PA) and the inhibitors PAI-1 and PAI-2 , and a decrease in tissue-type plasminogen activator (t-PA). In the p resent study we evaluated the prognostic significance of these paramet ers to the overall survival of patients with colorectal cancer, in con junction with several major clinicopathological parameters like age, g ender, differentiation grade, and Dukes' stage. Univariate analyses re vealed that a low t-PA antigen level, low t-PA activity, and high u-PA /t-PA antigen ratio in normal mucosa and a high u-PA and PAI-2 antigen level in carcinomas are prognostic for a poor overall survival of pat ients with colorectal cancer. The prognostic value of t-PA antigen and activity in normal mucosa, the antigen ratio of u-PA in carcinoma (C) and t-PA in corresponding normal (N) mucosa [u-PA(C)/t-PA(N) antigen ratio], and PAI-2 antigen in carcinomas was found to be independent fr om clinicopathological parameters by multivariate analyses. These obse rvations illustrate the clinical importance of the plasminogen activat ion cascade at the tissue level in colorectal cancer invasion, metasta sis, and survival.