IMMUNOFLUOROMETRIC ANALYSIS OF P53 PROTEIN AND PROSTATE-SPECIFIC ANTIGEN IN BREAST-TUMORS AND THEIR ASSOCIATION WITH OTHER PROGNOSTIC INDICATORS

Mutation and overexpression of p53 occurs in 20-40% of breast cancers and has been shown to be an independent prognostic indicator. Recently we have demonstrated prostate-specific antigen (PSA) expression in br east tumours to be suggestive of favourable prognosis, but quantitativ e relationships between PSA and p53, and between these and other progn ostic factors in breast cancer, have not been investigated. Time-resol ved immunofluorometric procedures were used to quantify both p53 prote in and PSA in 200 breast tumour extracts, which were also assayed for oestrogen (ER) and progesterone receptors (PGR), epidermal growth fact or receptors (EGFR), cathepsin D and HER-2/neu, and characterised for S-phase fraction and DNA ploidy. Weak Spearman correlations were found between p53 and ER (r = - 0.18, P = 0.010), PGR (r = - 0.15, P = 0.03 85) and S-phase fraction (r = 0.17, P = 0.016), while PSA was correlat ed only with PGR (r = 0.16, P = 0.025). Wilcoxon rank sum analysis rev ealed that levels of ER (P = 0.0001), PGR (P = 0.0001), S-phase fracti on (P = 0.0001) and EGFR (P = 0.0014) differed significantly between t he two groups categorised as p53 negative or p53 positive. Tumours cla ssifed as PSA negative or PSA positive were found to differ with respe ct to PGR (P = 0.0091) and S-phase fraction (P = 0.011) in a similar a nalysis. Contingency tables indicated significant negative association s between the status of p53 and that of ER (P = 0.003) and PGR (P = 0. 001) and between PSA and S-phase fraction (P = 0.012), and positive as sociations between p53 and EGFR (P = 0.017), HER-2/neu (P = O.OO8), S- phase fraction (P = 0.001) and aneuploidy (P = 0.007), and between PSA and both ER (P = 0.061) and PGR (P = 0.010). No significant associati ons were found between p53 and PSA. Our results demonstrate that the p resence of p53 in breast tumours relates to several other variables wh ich are suspected to predict aggressive tumour phenotypes and that the presence of PSA relates to variables associated with good prognosis.