PROGNOSTIC SIGNIFICANCE OF THE CO-EXPRESSION OF p53 AND c-erbB-2 PROTEINS IN BREAST CANCER

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Abstract
The immunohistochemical expression of p53 and c‐erbB‐2 gene proteins was examined in a series of 130 breast adenocarcinomas. This study intended to investigate whether the frequency of the altered expression of the tumour suppressor gene p53 and the overexpression of the oncogene c‐erbB‐2 in breast cancer tissue cells correlated with other variables known to affect the biological behaviour of these tumours and the overall survival of the patients (median follow‐up time: 6 years). The expression of p53 protein and c‐erbB‐2 gene product was evaluated immunohistochemically. Expression of p53 protein was detected in 30 (23 per cent) of the neoplasms examined, while 26 (20 per cent) out of the 130 cases demonstrated positive c‐erbB‐2 immunoreactivity. There was a statistically significant association between p53 protein expression and primary tumour size, lymph node involvement, and oestrogen receptor positivity. The incidence of c‐erbB‐2 positivity was significantly correlated with high tumour grade, axillary node invasion, large tumour size, and the absence of steroid receptors. p53 immuno‐expression was clearly associated with c‐erbB‐2 protein overexpression. Concomitant p53 and c‐erbB‐2 positive immunolabelling, which emerged in 14 out of the 130 cases (10·7 per cent), was clearly associated with high grade, large size, positive nodal status, ductal infiltrating (NOS) histological type, and low values of progesterone receptors. Overall survival of patients was not significantly related to the immunoreactivity of either p53 or c‐erbB‐2 considered separately, whereas there was a clearly significant trend to worse overall prognosis in cancers with double p53/c‐erbB‐2 positive phenotype. The simultaneous immunodetection of p53/c‐erbB‐2 appears to have greater negative prognostic relevance than their separate expression.