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.


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.
Offersen
Birgitte Vrou
BV
Department of Experimental Clinical Oncology, Aarhus University Hospital, Nørrebrogade 44, Bld. 5, DK-8000 Aarhus C, Denmark. bvo@oncology.dk
Pfeiffer
Per
P
Andreasen
Peter
P
Overgaard
Jens
J
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000473:pathology; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator