PROGNOSTIC VALUE OF P53 AND UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN NODE-NEGATIVE HUMAN BREAST CANCERS

We measured the levels of p53 and urokinase-type plasminogen activator (uPA) in 634 tumor tissues from 634 different node-negative primary b reast cancer patients who underwent locoregional surgery in the Center Oscar Lambret between July 1989 and September 1994, p53 and uPA were assayed using commercially available kits in cytosols prepared for est radiol receptor (ER) and progesterone receptor (PgR) assays, The optim um clinical thresholds were chosen for prognostic studies: 4 ng/ml for p53 and 0.5 ng/ml for uPA, p53 was elevated in 13.7% of the tumors, a nd uPA was elevated in 27.5% of the tumors; they were negatively relat ed (chi(2) test) to ER and PgR and positively related to histoprognost ic grading (HPG) and tumor diameter, uPA was negatively correlated to ER and PgR, and p53 and uPA were positively correlated to each other ( P = 0.0001; Spearman test), In the prognostic studies, the 316 patient s who did not receive adjuvant chemotherapy were included to avoid tre atment interference; this number corresponds to all of the patients op erated on between 1989 and 1992. The mean duration of follow-up of liv ing patients was 4 years. In overall survival studies, Cox univariate analyses demonstrated a prognostic value of p53 (P = 0.011; risk ratio , 1.59), uPA (P = 0.038; risk ratio, 2.32), PgR, HPG, and tumor diamet er, In Cox multivariate analyses, only HPG had a statistically signifi cant prognostic value. In relapse-free survival studies, univariate an alyses demonstrated prognostic values of uPA (P = 0.0011) and of age, and both parameters retained their prognostic value in multivariate an alyses (uPA: P = 0.0004), This study demonstrates not only that p53 an d uPA have prognostic value but also that these two parameters are lin ked to other classical clinical, histological, or biological prognosti c parameters, as well as to each other, Moreover, because uPA is of pr ognostic value in multivariate relapse-free survival studies, uPA is a n important prognostic factor in node-negative breast cancer patients.