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Gastroenterology Research and Practice
Volume 2017, Article ID 6504960, 10 pages
Research Article

Tumor Budding, uPA, and PAI-1 in Colorectal Cancer: Update of a Prospective Study

1Institute of Pathology, Klinikum Augsburg, Augsburg, Germany
2Institute of Laboratory Medicine and Microbiology, Klinikum Augsburg, Augsburg, Germany
3Clinical and Population-Based Cancer Registry Augsburg, Augsburg, Germany
4Department of Visceral Surgery, Klinikum Augsburg, Augsburg, Germany

Correspondence should be addressed to Bruno Märkl; ed.grubsgua-mukinilk@lkream.onurb

Received 5 September 2016; Revised 18 December 2016; Accepted 5 January 2017; Published 12 February 2017

Academic Editor: Mitsuro Kanda

Copyright © 2017 Bruno Märkl et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Aims. The prognostic role of the proteases uPA and PAI-1, as well as tumor budding, in colon cancer, has been investigated previously. Methods. We provide 6-year follow-up data and results of the validation set. The initial test set and validation set consisted of 55 colon cancers and 68 colorectal cancers, respectively. Tissue samples were analyzed for uPA and PAI-1 using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA). Tumor budding was analyzed on cytokeratin-stained slides. Survival analyses were performed using cut-offs that were determined previously. Results. uPA was not prognostic for outcome. PAI-1 showed a trend towards reduced cancer specific survival in PAI-1 high-grade cases (68 versus 83 months; ). The combination of high-grade PAI-1 and tumor budding was associated with significantly reduced cancer specific survival (60 versus 83 months; ). After pooling the data from both sets, multivariate analyses revealed that the factors pN-stage, V-stage, and a combination of tumor budding and PAI-1 were independently prognostic for the association with distant metastases. Conclusions. A synergistic adverse effect of PAI-1 and tumor budding in uni- and multivariable analyses was found. PAI-1 could serve as a target for anticancer therapy.