Plasminogen Activation System in Rectal Adenocarcinoma

Anticancer Res. 2015 Nov;35(11):6009-15.

Abstract

Background: The purpose of the present study was to determine the extent of expression of proteins that are the elements of the plasminogen activation system, i.e. urokinase plasminogen activator (uPA), receptor of uPA (uPAR), plasminogen activating inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in the primary site of rectal adenocarcinoma, as well as in lymph node metastases, and their correlation with clinical and pathological data.

Materials and methods: The study material consisted of archival paraffin blocks from 108 patients with confirmed oncological diagnosis, treated in 2002 and 2003 in the Lower Silesian Oncology Centre in Wroclaw. This material was used for immunohistochemical reactions with antibodies against uPA, uPAR, PAI-1 and tPA. The extent of expression was evaluated semi-quantitatively based on the immunoreactive score according to Remmele and Stegner. The obtained results were correlated with clinical and pathological data: stage of the disease (modified Dukes' classification of Astler and Coller), grade of histological malignancy, event-free survival and overall survival.

Results: It was found that cytoplasmic expression of uPA, uPAR, PAI-1 and tPA was higher in cells of tumor and metastases of perienteric lymph nodes in comparison to normal rectal tissues. Positive correlation was shown between expression of PAI-1 and tPA, uPA and uPAR, as well uPA and PAI-1 (r=0.70, r=0.77 and r=0.34, respectively; p<0.05 for all). Additionally, in patients with low and moderate expression of uPA and uPAR, the overall survival rate was higher in comparison to patients with high expression of the studied markers.

Conclusion: The intensity of expression of uPA and uPAR might be a prognostic factor of survival time for patients with primary rectal adenocarcinomas.

Keywords: PAI-1; Plasminogen activation system; rectal adenocarcinoma; tPA; uPA; uPAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Plasminogen / metabolism*
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Prognosis
  • Receptors, Urokinase Plasminogen Activator / metabolism*
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology
  • Survival Rate
  • Tissue Plasminogen Activator / metabolism*
  • Urokinase-Type Plasminogen Activator / metabolism*

Substances

  • Biomarkers, Tumor
  • Plasminogen Activator Inhibitor 1
  • Receptors, Urokinase Plasminogen Activator
  • SERPINE1 protein, human
  • Plasminogen
  • PLAT protein, human
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator