Serine proteinase activation in esophageal cancer

Background: Activation of the plasminogen/plasmin system seems to contribut e to tumor aggressiveness and shorter post-operative survival. In the prese nt study we examined the relation of uPA (urokinase plasminogen activator), uPAR (uPA receptor) and PAI-1 (plasminogen activator inhibitor type 1) to the biological growth behavior of esophageal cancer, as well as their influ ence on survival in esophageal cancer. Materials and Methods: The expressio n and distribution of uPA, uPAR and PAI-1 were analyzed by Northern blot an alysis and immunostaining in 41 resected esophageal cancers and in normal e sophagi. Results: Northern blot analysis revealed a 5.0-, 3.6- and 5.4-fold increase in uPA, uPAR, and PAI-1 mRNA levels in esophageal cancer, respect ively, in comparison to normal controls (p <0.01). These mRNA moieties were concomitantly increased in 86% of the tumors. uPA activity was 2.3-fold in creased in esophageal cancer compared with normal controls (p <0.01). Stati stical analysis revealed no differences in uPA, uPAR and PAI-1 immunoreacti vity between well-differentiated, moderately-differentiated and poorly-diff erentiated tumors. Furthermore, survival analysis showed no difference in p atients whose tumors exhibited positive uPA and uPAR immunostaining (median 11 months, range 4-36 months) versus patients whose tumors exhibited negat ive uPA and uPAR immunostaining (median 11 months, range 3-51 months). Conc lusion: Our data revealed that overexpression of uPA, uPAR and PAI-1 is oft en present in human esophageal carcinomas. However, up-regulation of these factors is not correlated with tumor differentiation or survival. These fin dings indicate that, unlike other tumors, uPA, uPAR and PAI-1 seem not to b e prognostic markers for esophageal carcinomas.