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Reviews |
1 Department of Nuclear Medicine, St. Vincent’s University Hospital, Dublin 4, and Department of Surgery and Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin 4, Ireland.
Address for correspondence: Department of Nuclear Medicine, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. Fax 353-1-2696018; e-mail Michael.J.Duffy{at}ucd.ie.
Background: For optimum management of patients with cancer, accurate assessment of prognosis is essential. The primary determinant of outcome in malignancy is the formation of distant metastases. Urokinase plasminogen activator (uPA) is a serine protease causally involved in invasion and metastasis.
Content: Data from model systems show that uPA is unequivocally involved in cancer dissemination. Consistent with its role in metastasis, multiple independent groups have shown that high uPA concentrations in primary breast cancers correlate with poor prognosis. For determining outcome, the prognostic impact of uPA was both independent of traditionally used factors and prognostic in patients with axillary node-negative disease. Paradoxically, high concentrations of plasminogen activator inhibitor (PAI-1), an endogenous inhibitor of uPA, also correlate with poor prognosis in patients with breast cancer, including the subgroup with node-negative disease. The prognostic value of uPA/PAI-1 in axillary node-negative breast cancer patients was recently confirmed in both a prospective randomized trial and a pooled analysis, i.e., two different level 1 evidence (LOE-1) studies.
Conclusions: uPA and PAI-1 are among the first biological prognostic factors to have their clinical value validated using LOE-1 evidence studies. Determination of these analytes may help identify low-risk node-negative breast cancer patients for whom adjuvant chemotherapy is unnecessary.
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M. Jo, K. S. Thomas, L. Wu, and S. L. Gonias Soluble Urokinase-type Plasminogen Activator Receptor Inhibits Cancer Cell Growth and Invasion by Direct Urokinase-independent Effects on Cell Signaling J. Biol. Chem., November 21, 2003; 278(47): 46692 - 46698. [Abstract] [Full Text] [PDF]
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