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

• Published in: British Journal of Cancer 1999-04, Vol.80 (1-2), p.167-174
• Main Authors: Jahkola, T, Toivonen, T, Smitten, K von, Virtanen, I, Wasenius, V-M, Blomqvist, C
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers; Biomedical and Life Sciences; Biomedicine; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer Research; Cathepsin D - metabolism; Drug Resistance; Epidemiology; Female; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Mammary gland diseases; Medical sciences; Molecular Medicine; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oncology; Plasminogen Activator Inhibitor 1 - metabolism; Prognosis; Regular; regular-article; Tenascin - metabolism; Tumors; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0007-0920; 1476-5381; 1532-1827
• 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.