Tumour budding, uPA and PAI-1 are associated with aggressive behaviour in colon cancer

J Surg Oncol. 2010 Sep 1;102(3):235-41. doi: 10.1002/jso.21611.

Abstract

Aims: The proteases PAI-1 and uPA play a major role in extracellular matrix degradation, which facilitates tumour progression. Tumour budding is a histomorphological expression of enhanced tumour cell migration.

Materials and methods: To investigate their prognostic value for and correlation with colon cancer, a prospective study was performed. We analysed tissue levels of uPA and PAI-1 of 55 colon cancer tumours employing a commercially available enzyme-linked immunosorbent assay (ELISA). Tumour budding was analysed on cytokeratin-stained slides.

Results: There was a strong correlation between uPA and tumour budding (R = 0.440; P < 0.001). uPA levels were increased in high grade tumours, whereas PAI-1 was elevated in cases with venous invasion (P = 0.004 and P = 0.028). PAI-1 values and tumour budding are associated significantly with the occurrence of distant metastases (P < 0.001 and P = 0.034, respectively). Tumour budding was significantly associated with lymph node metastases (P = 0.034). Multivariate analysis revealed PAI-1 and lymph node metastases to be independently predictive of distant metastases (P = 0.007 and P = 0.004, respectively).

Conclusions: The results of our study show that tumour budding and the plasmin/plasminogen system are related. PAI-1 was independently predictive for the occurrence of distant metastasis.

MeSH terms

  • Aged
  • Cell Movement
  • Colonic Neoplasms / pathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / analysis*
  • Plasminogen Activator Inhibitor 1 / physiology
  • Prospective Studies
  • ROC Curve
  • Urokinase-Type Plasminogen Activator / analysis*
  • Urokinase-Type Plasminogen Activator / physiology

Substances

  • Plasminogen Activator Inhibitor 1
  • Urokinase-Type Plasminogen Activator