This study was designed to evaluate whether patients with an unfavorable breast cancer prognosis could be identified by p53 protein overexpression detected by a quantitative enzyme-linked immunoabsorbent assay (ELISA).
PATIENTS AND METHODS
Extracts from 998 breast carcinomas were assayed for p53 protein by an ELISA that used both DO-1 monoclonal and CM-1 polyclonal antibodies. Relative risks (RRs) for cancer relapse and death after 6 years of follow-up for patients with p53-positive tumors based on different dichotomization criteria were determined by multivariate Cox regression, adjusted for patient age, tumor size, S-phase fraction, estrogen (ER) and progesterone (PR) receptor concentrations, DNA ploidy, and lymph node metastases. Disease-free (DFS) and overall (OS) survival probabilities of p53-positive and p53-negative groups, using a median cutoff, were also estimated by the Kaplan-Meier method and the log-rank test. These analyses were performed for all patients and for subgroups defined by ER status, node status, and primary postoperative treatment.
Univariate analysis showed that p53 concentrations that exceeded the median indicated significantly increased risks for relapse (P < .01) and death (P = .02). Multivariate analyses confirmed these observations (RR = 1.40; P = .02 for DFS and RR = 1.50; P < .01 for OS) and showed trends for increasing risks for relapse (P = .02) and death (P = .06) when p53 was considered as a four-level categoric variable, and identified p53 positivity as a significant predictor of outcome in node-positive patients (RR = 1.67; P < .01 and RR = 2.10; P < .01 for DFS and OS, respectively), ER-positive patients (RR = 1.45; P = .02 and RR = 1.50; P = .01 for DFS and OS, respectively), and in patients treated with chemotherapy (RR = 1.73; P = .04 for relapse and RR = 2.04; P = .03 for death).
Assessment of p53 overexpression by ELISA, easily incorporated into the routine biochemical work-up of breast tumors, may be an independent predictor of reduced survival of breast cancer patients.