Tumour Budding, uPA and PAI-1 Are Associated With Aggressive Behaviour in Colon Cancer

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. J. Surg. Oncol. 2010;102:235-241. (C) 2010 Wiley-Liss, Inc.