Urokinase-type plasminogen activator and inhibitor as prognostic markers in patients with non-small cell lung cancer and lymph node metestases

Background: Several biological markers have shown their usefulness in patients with lung cancer. Urokinase-type plasminogen activator (u-PA) is a member of the serine protease, an extracellular matrix protease strictly related to tumor aggression. It is localized on the tumor cells surface by binding to a specific receptor (u-PAR), which regulates the proteolytic activity around the cells. Plasminogen activator inhibitor 2 (PAI-2) regulates the u-PA activity. The expression of u-PA and PAR is elevated in malignant tumors, while low levels of PAI-2 expression correlates with the presence of metastases. We retrospectively assayed the expression of u-PA, u-PAR, and PAI-2 in specimens from non-small cell lung carcinoma (NSCLC), with the aim of evaluating possible relationship between these prognostic markers and the presence of lymph node metastasis. Patients and methods: Paraffin-embedded archival tumor tissues from 59 patients with NSCLC were used to assess by immunohistochemical staining expressions of u-PA and u-PAR, and to measure by enzyme-linked immunosorbent assay levels of PAI-2 antigen. The analysis was performed by reverse transcriptase polymerase chain reaction (RT-PCR). Patients were 42 (71.2%) males and 17 (28.8%) females, with a median age of 62 years (range 54-68). LN metastases were found in 25 (42.3%, Group A) patients, while 34 (57.7%, Group B) were node-negative (pN0). A positive-staining area of more than 10% was considered as a positive result. The Pearson chi-square (\u3c72) test was used to compare data. Results: Positive markers (A vs. B) were found in 15 of 25 vs. 24 of 34 (u-PA), 10 of 25 vs. 24 of 34 (u-PAR), and 13 of 25 vs. 23 of 34 (PAI-2) specimens, respectively. A significant relationship between u-PAR positivity and LN metastasis (\u3c72=5.52, p=0.018) was found, while both u-PA (\u3c72=0.72 p=0.39) and u-PAR PAI-2 (\u3c72=1.48, p=0.22) were not related to LN status. Conclusions: In patients with NSCLC, u-PAR seems to be the key molecule for extracellular matrix degradation enzyme and the target molecule of cancer metastasis prevention, representing a sensitive marker of prognosis