Cathepsin-D, urokinase plasminogen activator and type-1 plasminogen activator inhibitor in early breast cancer: an immunohistochemical study of prognostic value and relations to tenascin-C and other factors

Br J Cancer. 1999 Apr;80(1-2):167-74. doi: 10.1038/sj.bjc.6690336.


Cytosolic determinations of cathepsin-D (cath-D), urokinase plasminogen activator (uPA) and its specific inhibitor PAI-1 have shown an association with adverse prognosis in breast cancer. Our aim was to study the distribution of these markers in small axillary node-negative breast carcinomas using immunohistochemistry and relate the semiquantitative results to known prognostic factors, the expression of tenascin-C (Tn-C) in invasion border of the tumour and prognosis. All the 158 women (159 tumours) were treated with breast conserving surgery and postoperative radiotherapy. Cytoplasmic immunoreactivity for cath-D was seen in carcinoma cells in 47% and in stromal cells in 44%. Nearly all tumours expressed uPA and PAI-1, which were categorized to cytoplasmic expression in carcinoma cells and diffuse stromal expression and quantified -/+/++/ and further dichotomized for purposes of analysis. Expression of uPA and PAI-1 in stromal fibroblasts was recorded as -/+. Cytoplasmic and stromal cell cath-D contents were associated with grade, proliferation, Tn-C expression in the tumour invasion border and the development of distant metastasis. In multivariate analysis stromal cath-D proved to be an independent prognostic factor for metastasis. Stromal expression of uPA was associated with an increased risk of local recurrence; otherwise high levels of uPA did not associate with other prognostic factors nor with prognosis. Fibroblastic expression of PAI-1 showed an association with both local and distant disease recurrence. However, no consistent association between the immunohistochemically quantified uPA and PAI-1 and prognosis was found. In conclusion, immunohistochemical determination of cath-D seems to be a viable method to predict a higher risk of metastasis but not local recurrence in small axillary node-negative breast carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cathepsin D / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Prognosis
  • Tenascin / metabolism*
  • Urokinase-Type Plasminogen Activator / metabolism*


  • Biomarkers
  • Plasminogen Activator Inhibitor 1
  • Tenascin
  • Urokinase-Type Plasminogen Activator
  • Cathepsin D