PAI-1 polymorphism and expression of uPA, PAI-1 and COX-2 in breast cancer

Abstract

9674 Background: The molecular components of Plasminogen Activator system, Urokinase-type Plasminogen Activator (uPA) and its inhibitor PAI-1, are involved in tumor progression and have prognostic value in early breast cancer (BC) patients. The -675 4G/5G polymorphism of the PAI-1 promoter gene is associated with different activity levels of PAI-1 in serum. Cycloxigenase-2 (COX-2) expression is associated with poor prognosis in early BC. In addition, it has been shown that COX-2 modulates uPA expression. We aimed at studying the PAI-1 polymorphism together with the immunohistochemical expression of uPA, PAI-1 and COX-2 in BC patients Methods: Blood samples from a consecutive series of 199 BC patients were collected and PAI-1 -675 4G/5G polymorphism was analyzed by PCR technique. Immunohistochemical expression of uPA, PAI-1, COX-2, HER-2/neu, and MIB-1/Ki-67 was evaluated in the tissue sample of primitive BC. A score combining intensity and percentage of cellular immunoreactivity, was used to assess the staining of uPA, PAI-1, and COX-2. uPA and PAI-1 positivity was evaluated in tumor cells and stromal fibroblasts. Results: The 4G allele was associated with regional lymph node involvement (P=.04). No statistically significant association was found between genotype and immunohistochemical expression of uPA, PAI-1 and COX-2. uPA immunostaining directly correlated with estrogen receptor expression (P=.03). Negative uPA score was associated with negative hormonal receptor expression, high tumor grade, and high MIB-1/Ki-67 expression (p<.05). PAI-1 score directly correlated with COX-2 expression (P=.02), and strong PAI-1 immunostaining was associated with moderate/strong expression of COX-2 (P=.006). Tumors with PAI-1 positive fibroblasts showed higher MIB-1/Ki-67 expression (P=.02). Moderate/strong COX-2 expression was associated with HER-2/neu overexpression (P=.02). Conclusions: These findings suggest that BC patients carrying the 4G allele of the PAI-1 promoter may have an increased probability of axillary lymph node involvement. In addition, our data support a possible interaction between Plasminogen Activator and COX-2 systems. No significant financial relationships to disclose.