Background: Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) determined by ELISA from fresh-frozen tumor tissue have been evaluated as prognostic factors in prospectively randomized trials in node-negative breast cancer. However, uPA and PAI-1 mRNA expression might reveal new clinically relevant information using paraffin-embedded tumor tissue.

Methods: We evaluated uPA and PAI-1 mRNA expression with the Affymetrix HG-U 133A array also within molecular subgroups of breast cancer in a finding cohort of breast cancer patients (cohort A; n = 548). We validated mRNA expression in a cohort of HER2 positive breast cancer patients (cohort B, n = 347). For uPA and PAI-1, mRNA values below and above the median were compared in two different probesets. “Luminal”, “triple-negative” and “HER2 positive” subcohorts were defined by ESR1 and ERBB2 mRNA expression using pre-defined cut-offs.

Results: In cohort A, elevated PAI-1 mRNA expression was associated with shorter disease-free survival (DFS) and overall survival (OS), elevated uPA mRNA expression was associated with shorter OS. Regarding different molecular subgroups, 71% (n = 388) of tumors had a luminal, 13% (n = 69) a HER2 positive and 17% (n = 91) a triple-negative subtype. Only in the HER2 positive subgroup, elevated PAI-1 mRNA expression was associated with shorter disease-free survival and overall survival (p = 0.003 for DFS and p = 0.012 for OS). Same results were found for uPA in HER2 positive patients (DFS, p = 0.027 and OS, p = 0.011). In contrast, no association between both markers and DFS and OS could be seen in the luminal or triple-negative subgroups. In the HER2 positive validation cohort B elevated uPA and PAI-1 mRNA expression showed a strong association with shorter DFS (p = 0.013 for PAI-1, p = 0.001 for uPA).

Conclusion: Results of this study demonstrate that the prognostic impact of uPA and PAI-1 mRNA expression was observed mainly in patients with HER2 positive tumors.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-44.