Association of uPA, PAI-1, and uPAR in Nipple Aspirate Fluid (NAF) with Breast Cancer

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Abstract
PURPOSE Urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI-1), and uPA receptor (uPAR) are prognostic factors in various cancer types, especially breast cancer. Less is known about the usefulness of these markers in breast cancer diagnosis. We sought to determine (1) whether uPA, PAI-1, and uPAR were detectable in breast nipple aspirate fluid (NAF), a physiologic fluid produced by the breast and collected noninvasively, and (2) the association of these markers in NAF with the presence of breast cancer. PATIENTS AND METHODS One hundred twenty NAF specimens were collected from women with and women without breast cancer. uPA, PAI-1, and uPAR expression in NAF was measured by enzyme-linked immunosorbent assay. RESULTS Median NAF PAI-1, but not uPA or uPAR, expression was higher in subjects with breast cancer than in those without breast cancer, regardless of whether expression was controlled for total NAF protein level. Median expression of PAI-1 per milligram of total NAF protein was higher in both premenopausal and postmenopausal women who had breast cancer than in women who did not. A multiple logistic regression model that included age, race, menopausal status, uPA, PAI-1, and uPAR level to differentiate patients with regard to cancer risk revealed that uPA, PAI-1, and age were each associated with risk (P ≤ 0.019). Women whose NAF contained elevated uPA and PAI-1 levels were more likely to have cancer than women in whom both markers were not elevated. DISCUSSION Our data suggest that PAI-1, alone or in combination with uPA, may be useful as a noninvasive biologic marker to aid in the detection of breast cancer.

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