Summary Recent studies have suggested that insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) may be implicated in the development and progression of breast cancer. Prostatespecific antigen (PSA), a serine protease, may play a role in the regulation of IGFs' function through cleavage of IGFBP-3, resulting in release of active IGFs from IGFBP-3. As IGFs, IGFBPs and PSA are all present in breast cancer, possible associations among these proteins were speculated. In this study, we have measured PSA, IGF-I, IGF-II, IGFBP-1 and IGFBP-3 in tumour tissue cytosols from 200 women with primary breast cancer, and have examined relationships between IGFs or IGFBPs and PSA along with other markers, including p53 protein, steroid hormone receptors (oestrogen and progesterone), cathepsin-D, epidermal growth factor receptor, Her-2/neu protein, S-phase fraction and DNA ploidy. Correlations or associations between PSA and IGF-I, IGF-II, IGFBP-1 or IGFBP-3 were not observed. IGF-II was positively correlated with both IGFBP-3 and IGFBP-1. IGF-I was not associated with either of the two binding proteins, nor with IGF-II. Both IGF-II and IGFBP-3 were inversely associated with the oestrogen receptor, and IGFBP-3 was also positively associated with S-phase fraction. Our finding of IGF-II and IGFBP-3 in association with unfavourable prognostic indicators of breast cancer suggests that IGFs may be involved in the progression of breast cancer.

Summary p53 protein, which accumulates intracellularly in over half of all human tumours, has also been reported to be present in the sera of patients with various malignancies, including lung cancer. Using a quantitative immunoassay, we measured p53 protein concentrations in 216 sera from 114 lung cancer patients of whom 75 provided matched lung tumour tissues, which were also assayed for p53 protein. p53 protein levels above the detection limit of 0.04 ng ml-' were detected in only two sera from lung cancer patients (0.14 ng ml-1 and 0.27 ng ml-1), but not in any of 13 sera from non-malignant lung disease patients or in 100 sera from normal non-diseased individuals. The presence of these apparent traces of serum p53 protein concentrations could not be related either to the p53 protein expression status of the primary lung tumours or to the tumour stage, grade or histological type. By pretreating these two sera with anti-p53 antibody linked to solid phase, and by the addition of mouse serum to neutralise possible heterophilic antibodies, the signals arising from these sera were shown to be non-specific and possibly caused by heterophilic antibodies. We conclude that our data do not support previous reports of p53 protein in the sera of lung cancer patients. Since immunoassays are subject to numerous sources of interference in serum, including heterophilic antibodies, we suggest that the results of p53 protein analysis of serum specimens should be interpreted with caution.

Suman 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 breast tumours to be suggestive of favourable prognosis, but quantitative relationships between PSA and p53. and between these and other prognostic factors in breast cancer, have not been investigated. Time-resolved immunofluorometric procedures were used to quantify both p53 protein and PSA in 200 breast tumour extracts, which were also assayed for oestrogen (ER) and progesterone receptors (PGR), epidermal growvth factor 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 = 0.0385) and S-phase fraction (r = 0.17. P = 0.016). while PSA was correlated only with PGR (r = 0.16. P = 0.025). Wilcoxon rank sum analysis revealed that levels of ER (P = 0.0001), PGR (P = 0.0001).S-phase fraction (P = 0.0001) and EGFR (P= 0.0014) differed significantly between the two groups categorised as p53 negative or p53 positive. Tumours classifed as PSA negative or PSA positive were found to differ with respect to PGR (P =0.0091) and S-phase fraction (P = 0.011) in a similar analysis. Contingency tables indicated significant negative associations betweeh 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 associations between p53 and EGFR (P = 0.017), HER-2 neu (P = 0.008). 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 associations were found between p53 and PSA. Our results demonstrate that the presence of p53 in breast tumours relates to several other variables which are suspected to predict aggressive tumour phenotypes and that the presence of PSA relates to variables associated with good prognosis.

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