Accumulation of uPA-PAI-1 complexes inside the tumour cells is associated with axillary nodal invasion in progesterone-receptor-positive early breast cancer.

Abstract

Both urokinase-like plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor (PAI-1), as well as uPA–PAI-1 complexes, have been identified as important prognostic factors in breast cancer. We have recently reported that the latter are identifiable inside breast cancer cells by means of immunohistochemistry. Using this technique, we have studied a series of 212 early (pT1) unifocal breast cancers and have correlated the expression of uPA–PAI-1 complexes, together with other clinical and biological features (histologic variety, histologic and nuclear grade, hormone receptors, Ki67 labelling index, c-erb-B2-, p53- and CD44std-expression) with or without the occurrence of axillary node invasion. In a logistic regression model, looking for associations with axillary metastasis, we found a statistically significant interaction between the presence of uPA–PAI-1 complexes and progesterone receptor positivity (P=0.04). A final model showed that the presence of uPA–PAI-1 complexes was a determinant factor for axillary metastasis among women carrying tumours expressing progesterone receptors. In these cases, the presence of uPA–PAI-1 complexes carried with it a nearly 14-fold risk of axillary node invasion (P=0.009). These results may indicate that small, hormone-receptor-positive breast cancers (with a theoretical good prognosis) may carry an elevated risk of nodal involvement if accumulation of uPA–PAI-1 complexes is shown inside their tumour cells by means of immunohistochemistry.