title: Tumour budding, uPA and PAI-1 are associated with aggressive behaviour in colon cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Institute of Pathology, Klinikum Augsburg, Augsburg, Germany. bruno.maerkl@klinikum-augsburg.de
authors.forename: B
authors.initials: B
authors.lastname: Märkl
authors.forename: I
authors.initials: I
authors.lastname: Renk
authors.forename: D V
authors.initials: DV
authors.lastname: Oruzio
authors.forename: H
authors.initials: H
authors.lastname: Jähnig
authors.forename: G
authors.initials: G
authors.lastname: Schenkirsch
authors.forename: C
authors.initials: C
authors.lastname: Schöler
authors.forename: W
authors.initials: W
authors.lastname: Ehret
authors.forename: H M
authors.initials: HM
authors.lastname: Arnholdt
authors.forename: M
authors.initials: M
authors.lastname: Anthuber
authors.forename: H
authors.initials: H
authors.lastname: Spatz
mesh_terms: D000368:Aged; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000502:physiology; D011446:Prospective Studies; D012372:ROC Curve; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis* / Q000502:physiology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator