Serine proteinase activation in esophageal cancer

W. H. Tang, H. Friess, P. B. Kekis, M. E. Martignoni, A. Fukuda, A. Roggo, A. Zimmermann, M. W. Büchler

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: Activation of the plasminogen/plasmin system seems to contribute to tumor aggressiveness and shorter post-operative survival. In the present 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 influence on survival in esophageal cancer. Materials and Methods: The expression and distribution of uPA, uPAR and PAI-1 were analyzed by Northern blot analysis and immunostaining in 41 resected esophageal cancers and in normal esophagi. 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, respectively, 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 increased in esophageal cancer compared with normal controls (p<0.01). Statistical analysis revealed no differences in uPA, uPAR and PAI-1 immunoreactivity between well-differentiated, moderately-differentiated and poorly-differentiated tumors. Furthermore, survival analysis showed no difference in patients whose tumors exhibited positive uPA and uPAR immunostaining (median 11 months, range 4-36 months) versus patients whose tumors exhibited negative uPA and uPAR immunostaining (median 11 months, range 3-51 months). Conclusion: Our data revealed that overexpression of uPA, uPAR and PAI-1 is often present in human esophageal carcinomas. However, up-regulation of these factors is not correlated with tumor differentiation or survival. These findings indicate that, unlike other tumors, uPA, uPAR and PAI-1 seem not to be prognostic markers for esophageal carcinomas.

Original languageEnglish
Pages (from-to)2249-2258
Number of pages10
JournalAnticancer Research
Volume21
Issue number4 A
StatePublished - 2001
Externally publishedYes

Keywords

  • Immunohistochemistry
  • Northern blot analysis
  • Plasminogen activator inhibitor
  • Urokinase plasminogen activator
  • Urokinase plasminogen activator receptor

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