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Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination.
Br J Cancer. 1999 Oct; 81(3):490-5.BJ

Abstract

p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan-Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P = 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(-)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(-) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone.

Authors+Show Affiliations

Section of Cancer Prevention and Control, Feist-Weiller Cancer Center, Louisiana State University Medical Center, Shreveport 71130, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10507775

Citation

Yu, H, et al. "Enhanced Prediction of Breast Cancer Prognosis By Evaluating Expression of P53 and Prostate-specific Antigen in Combination." British Journal of Cancer, vol. 81, no. 3, 1999, pp. 490-5.
Yu H, Levesque MA, Clark GM, et al. Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination. Br J Cancer. 1999;81(3):490-5.
Yu, H., Levesque, M. A., Clark, G. M., & Diamandis, E. P. (1999). Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination. British Journal of Cancer, 81(3), 490-5.
Yu H, et al. Enhanced Prediction of Breast Cancer Prognosis By Evaluating Expression of P53 and Prostate-specific Antigen in Combination. Br J Cancer. 1999;81(3):490-5. PubMed PMID: 10507775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination. AU - Yu,H, AU - Levesque,M A, AU - Clark,G M, AU - Diamandis,E P, PY - 1999/10/3/pubmed PY - 1999/10/3/medline PY - 1999/10/3/entrez SP - 490 EP - 5 JF - British journal of cancer JO - Br J Cancer VL - 81 IS - 3 N2 - p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan-Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P = 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(-)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(-) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone. SN - 0007-0920 UR - https://www.unboundmedicine.com/medline/citation/10507775/Enhanced_prediction_of_breast_cancer_prognosis_by_evaluating_expression_of_p53_and_prostate_specific_antigen_in_combination_ L2 - https://doi.org/10.1038/sj.bjc.6690720 DB - PRIME DP - Unbound Medicine ER -