Prognostic value of uPA and p53 accumulation measured by quantitative biochemical assays in 1245 primary breast cancer patients: a multicentre study

The purpose of this retrospective multicentre study was to assess the progn ostic value of urokinase plasminogen activator (uPA) and p53 levels in a la rge series of primary breast cancer, using an automatic quantitative lumino metric method. Samples of 1245 operable breast tumours were collected from seven French institutions and patients were followed for a median of 75 mon ths. The median uPA and p53 levels assayed in cytosols by means of the immu noluminometric technique (LIA) were 0.31 and 0.20 ng mg(-1) of protein resp ectively. In univariate analysis, high levels of uPA and p53 were associate d with shorter disease-specific survival, disease-free interval, and distan t recurrence-free interval. The 5-year survival rates were 95.5% among pati ents with uPA values below the 20th percentile, and 77.5% in those with val ues above the 80th percentile. The 5-year survival rates were 91.0% in pati ents with p53 values below the 20th percentile, and 77.6% in those with val ues above the 80th percentile. In multivariate analysis, the risk of diseas e-related death increased with uPA levels after adjustment for tumour size, histological grade. lymph node involvement, and estrogen receptor status. A high level of uPA was also related to a shorter disease-free interval and distant recurrence-free interval. In node-negative patients,a high level o f uPA remained strongly related to the three outcomes. When adjusted for ot her prognostic factors, p53 was no longer significantly related to the outc omes. Given its rapidity and simple application to routinely prepared cytos ols, this LIA may be useful for evaluating the prognostic impact of uPA in primary breast cancer, particularly in node-negative patients. According to our results, the prognostic value of p53 accumulation is limited when uPA is included in multivariate analysis.