Urokinase plasminogen activator and plasminogen activator inhibitor type-1 in nonsmall-cell lung cancer: relation to prognosis and angiogenesis.

BACKGROUND: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) have previously been suggested as prognostic markers in nonsmall-cell lung carcinomas (NSCLC). We investigate whether uPA and PAI-1 are prognostic markers in NSCLC and whether they are related to angiogenesis.
MATERIALS AND METHODS: Frozen tumour tissue from surgical specimens from 118 previously untreated patients diagnosed with NSCLC in the period 1984-1991 were investigated. All patients were treated with surgery, and no chemo- or radiotherapy was given. UPA and PAI-1 levels were assessed using a sandwich ELISA method.
RESULTS: Both uPA and PAI-1 were independent of classical histopathological parameters as well as of microvessel density and vascular pattern. Using death within the first 5 years as endpoint, neither of the factors were prognostic markers in univariate analysis, however, significantly higher levels of uPA and PAI-1 were seen in tumours with an angiogenic vascular pattern. In multivariate analysis, high disease stage (P<0.0001), adenocarcinoma (P=0.007), old age (P=0.02), and presence of an angiogenic pattern (P=0.05) were identified as independent markers of death within 5 years.
CONCLUSIONS: The present study investigated the prognostic role of the protein levels of uPA and PAI-1 in 118 tumour specimens from patients diagnosed with NSCLC. Neither of the factors were identified as prognostic markers when evaluated with survival as endpoint. However, in tumours previously identified as non-angiogenic we found significantly lower contents of both uPA and PAI-1 as compared to angiogenic tumours, thus we hypothesize that uPA and PAI-1 stimulate angiogenesis in NSCLC.