Urokinase type plasminogen activator expression and its correlation with angiogenesis and lymph node metastasis in breast cancer

Abstract

Background: Search for prognostic marker in breast cancer is an area of ongoing research. uPA (Urokinase like plasminogen activator) system has been well documented in cancer invasion and metastasis and extensively researched over the years in different cancers. Familial uPAR (urokinase like plasminogen activator receptor) has been shown to promote promotes angiogenesis. Objective: To detect the expression of uPA in breast cancer patients and its correlation with established prognostic markers and Vascular Endothelial Growth Factor (VEGF) expression. Methods: Histologically proven cases of early breast cancer were included in the study who had not received any neo-adjuvant therapy. The patients were characterised based on age at diagnosis, menopausal status, parity, TNM stage. Size of tumor, type of cancer, grade of tumor, tumor necrosis, lymph nodes positive (from sections taken from lymph node), lymphovascular invasion (LVI) and immunohistological details such as hormonal status (ER, PR and HER-2/neu). The expression of VEGF and uPA was done with immunohistochemistry and correlation was analysed. Results: A total 30 histologically proven early breast cancer patients were included in the study with a mean age of 49.53±9.702 years (range 30-65 years). uPA was expressed in 90% of patients with a mean uPA IRS (immunoreactive score) of 3.567±1.85.The mean VEGF immunoreactive score was 4.16. The uPA expression was significantly associated with T-stage (p<0.001), axillary node (p=0.029), grade of tumor (p=0.028) and lymphovascular invasion (p=0.002) respectively. The positive correlation was found between uPA IRS score and larger tumor size (r=0.727, p<0.001) and number of positive lymph nodes (r=0.466, p=0.009). The correlation between uPA IRS with VEGF IRS was also found to be significant positively correlated (r=0.727, p<0.001). Conclusion: The results support the importance of uPA expression in breast cancer as a potential for prognosis estimation.