Mutant p53, EGF receptor and c-erbB-2 expression in human breast cancer.

p53 expression was studied in 111 primary breast cancers with a monoclonal antibody (PAb240) that reacts with an epitope in mutant p53. Epidermal growth factor receptors (EGFr) and oestrogen receptors (ER) measured by ligand binding, c-erbB-2 expression assessed by immunochemistry and lymph node status were compared with p53 staining. Fifty-nine tumours (53%) were positive for p53, and this correlated with EGFr expression (P less than 0.02), which is a known poor prognostic factor. Eighteen out of 59 p53+ tumours expressed c-erbB-2 versus 4 out of 52 p53- tumours assessed on paraffin sections. However, assessing c-erbB-2 by Southern blotting and immunochemistry on frozen sections showed that 20 out of 59 p53+ tumours overexpressed or had amplified c-erbB-2 compared with 15 out of 52 p53- tumours (not significant). Mean EGFr concentration in p53+ tumours was 31 fmol per mg of membrane protein versus 14 fmol mg-1 in p53- tumours. Cytoplasmic staining was the most frequent pattern found for p53, but some cases showed cytoplasmic plus nuclear staining, or focal cells with predominantly nuclear staining. Thus, abnormal p53 is the commonest oncogene abnormality described in breast cancer. The association with EGFr expression suggests that these oncogenes interact in the pathogenesis of breast cancer.