Markers of the uPA System and Common Prognostic Factors in Breast Cancer

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Abstract
The urokinase plasminogen activator (uPA) system includes uPA and plasminogen activator inhibitor types 1 (PAI-1) and 2 that mainly act by regulating extracellular matrix degradation, and it is involved in tumor progression. The –675 4G/5G polymorphism of the PAI-1 gene regulates PAI-1 activity in serum. We aimed at studying the –675 4G/5G polymorphism of the PAI-1 gene and uPA, PAI-1, and cyclooxygenase-2 (COX-2) immunohistochemical expression in a series of breast cancer cases. Homozygosity for the 4G allele of the PAI-1 gene was associated with node-positive breast cancer (P = .02). We showed a direct correlation between uPA and estrogen receptor expression (P = .03); negative uPA expression was associated with negative hormonal expression, high tumor grade, and high proliferation index (P < .05). A direct correlation was seen between uPA and PAI-1, uPA and COX-2, and PAI-1 and COX-2 expression (P < .05). Interaction between uPA and COX-2 systems in breast cancer deserves further study.

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