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

Abstract

SummaryThe purpose of this retrospective multicentre study was to assess the prognostic value of urokinase plasminogen activator (uPA) and p53 levels in a large series of primary breast cancer, using an automatic quantitative luminometric method. Samples of 1245 operable breast tumours were collected from seven French institutions and patients were followed for a median of 75 months. The median uPA and p53 levels assayed in cytosols by means of the immunoluminometric technique (LIA) were 0.31 and 0.20 ng mg -1 of protein respectively. In univariate analysis, high levels of uPA and p53 were associated with shorter disease-specific survival, disease-free interval, and distant recurrence-free interval. The 5-year survival rates were 95.5% among patients with uPA values below the 20th percentile, and 77.5% in those with values above the 80th percentile. The 5-year survival rates were 91.0% in patients with p53 values below the 20th percentile, and 77.6% in those with values above the 80th percentile. In multivariate analysis, the risk of disease-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 of uPA remained strongly related to the three outcomes. When adjusted for other prognostic factors, p53 was no longer significantly related to the outcomes. Given its rapidity and simple application to routinely prepared cytosols, 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.

Urokinase plasminogen activator: A prognostic marker in multiple types of cancer

“…In particular, in multiple studies, it has been found to be a marker of aggressiveness in node-negative patients (Table II). In this subgroup of patients, as with total populations, the prognostic impact of uPA is generally found to be independent of tumor size, grade, patient age, ER status, and progesterone receptor (PR) status [22,24,36]. In addition to the node-negative subgroup, uPA levels have been shown to correlate with patient outcome in node-positive, premenopausal, postmenopausal, and ER-positive subgroups [35].…”

“…As an indicator of patient outcome, most investigators find that the prognostic impact of uPA is independent of traditionally used markers such as axillary node status, tumor size, tumor grade, and estrogen receptor (ER) status [15,24,32,33]. In most studies with short-term followup, uPA is a more potent predictor of disease-free and overall survival than either tumor size or ER status and of similar strength to nodal status [32,33].…”

Prognostic significance of tumor-related proteases as a function of the estrogen receptor status

“…This decrease in uPA and PAI-1 production in ER-positive tumors has previously been reported. 18,32,33 At the gene level, a non-aggressive phenotype has been identified in cells exhibiting ER-positive expression and a lack of PAI-1 expression, whereas inversely, cells devoid of ER expression but positive for PAI-1 were shown to be invasive. 34 A potentially more aggressive subgroup of highly ER-positive BC might be in keeping with some previous observations of Thorpe and colleagues, who showed that the natural history of tumors with high ER levels is more deleterious.…”

Induction of p53 by Urokinase in Lung Epithelial Cells

“…Elaboration of these molecules influences two major features associated with lung neoplasia, including excessive proliferation of neoplastic cells and their capacity to invade normal tissues. It is now clear that the pathogenesis of lung neoplasia prominently involves expression of tumor suppressor protein p53 (22)(23)(24) as well as extracellular matrix degradation by uPA-mediated plasminogen activation (6,7,24). Among the plethora of potentially useful markers of tumor virulence that have been identified to date, both uPA and p53 appear to be promising (24,25).…”