FREE-FORM NEUTROPHIL ELASTASE IS AN INDEPENDENT MARKER PREDICTING RECURRENCE IN PRIMARY BREAST-CANCER

We have measured the immunoreactive neutrophil elastase (ir-NE) concentration in tumor extracts of 313 primary human breast cancers using an enzyme-linked immunosorbent assay recently developed and have evaluated its association with disease-free survival. This is a sensitive assay that enables rapid measurement of both free-form and alpha(1)-proteinase inhibitor (alpha(1)-PI)-complexed form of ir-NE. Breast cancer patients with high ir-NE concentrations had a significantly shorter disease-free survival (P = .013) than those with a low if-NE concentration at the cutoff point of 9.0 mu g/100 mg protein, which was determined in another group of 49 patients. In multivariate analysis, the ir-NE level was found to be an independent prognostic factor (relative risk = 2.2, P = .025) for disease recurrence in human breast cancer. Furthermore, when multivariate analysis was repeated with inclusion of each level of free-form and alpha(1)-PI-complexed form, the former level was an independent predictor of recurrence (relative risk = 2.5, P = .015), whereas the latter was not independently predictive (P = .43). These results support the hypothesis that this enzyme may play an active role in the tumor progression that leads to metastasis in human breast cancer.