Plasminogen activator inhibitor-1 (PAI-1) expression in relation to hypoxia and oncoproteins in clinical cervical tumors

Strahlenther Onkol. 2012 Dec;188(12):1139-45. doi: 10.1007/s00066-012-0216-y. Epub 2012 Nov 1.

Abstract

Purpose: Explore the role of plasminogen activator inhibitor-1 (PAI-1) in cervical cancer and its relationship to hypoxia and the expression of p53, Ku70/80, and cyclin D1.

Material and methods: The expression of PAI-1, cyclin D1, and p53, together with tumor oxygenation, were determined in 43 consecutive patients suffering from localized cervical carcinoma. Oncoprotein expression was determined by immunohistochemistry. Tumor oxygenation was measured using a polarographic probe system, "pO2 histography."

Results: PAI expression was considered negative in 32.6% and overexpressed in 18.6% of cases. Cyclin D1 showed a median expression of 5.0 (range 0-70). We observed a positive association between PAI expression and altered p53 (p = 0.049) and cyclin D1 (p = 0.020). An inverse association was detected between PAI and Ku70/80 expression (p = 0.042). Cyclin D1 staining increased according to tumor volume (r = 0.314, p = 0.009). We did not observe a significant association between PAI and hypoxia or other clinicopathological parameters.

Conclusion: The present results show that PAI-1 overexpression is associated with nonhomologous end-joining DNA repair down-regulation (low Ku70/80 expression) and with increased p53 and cyclin D1 expression, and they suggest that PAI-1 plays a role in the tumor behavior in cervical carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Nuclear / genetics*
  • Biopsy
  • Cell Hypoxia / genetics*
  • Cervix Uteri / pathology
  • Cyclin D1 / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunoenzyme Techniques
  • Ku Autoantigen
  • Middle Aged
  • Neoplasm Staging
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Prognosis
  • Prospective Studies
  • Tumor Suppressor Protein p53 / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*

Substances

  • Antigens, Nuclear
  • CCND1 protein, human
  • DNA-Binding Proteins
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Xrcc6 protein, human
  • Ku Autoantigen