ANTIGEN LEVELS OF UROKINASE PLASMINOGEN-ACTIVATOR AND ITS RECEPTOR ATTHE TUMOR-HOST INTERFACE OF COLORECTAL ADENOCARCINOMAS ARE RELATED TOTUMOR AGGRESSIVENESS

The distributions of urokinase and tissue plasminogen activators (uPA, tPA), uPA receptor (uPAR), and plasminogen activator inhibitors (PAI- 1, PAI-2) were studied immunohistochemically in two subsets of colorec tal adenocarcinomas with low and high aggressiveness, respectively: ni ne Dukes' stage A tumors with additional other good prognostic markers and 13 Dukes' stage C tumors with also other poor prognostic markers (referred to as Dukes' stage A and Dukes' stage C tumors). The results showed that these components of the tissue destructive plasminogen ac tivation system were accumulated at the invading front of the tumors. Both tumor groups showed accumulations of uPA, uPAR, and PAI-1 at the tumor-host interface compared with the location within the tumor epith elium and the adjacent normal mucosa and muscularis propria (all P < . 05). However, the uPA level at the tumor-host interface in the Dukes' stage C tumors was twice the level in the Dukes' stage A tumors (P < . 05). The uPAR level was also significantly higher in the Dukes' stage C tumors (P < .05), whereas the PAI-1 level was not significantly high er. This may indicate that uPA in more aggressive tumors exceeds the i nhibitory capacity represented by PAIs, resulting in enhanced tissue d estructive potential that promotes tumor invasion. uPA and uPAR antige n levels and the uPA/PAI-1 ratio at the tumor-host interface appeared to be related to tumor aggressiveness in colorectal cancer. Copyright (C) 1995 by W.B. Saunders Company