c-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer

Abstract

We examined c-erbB3 and c-erbB4 mRNA expression in 47 primary breast cancer samples by simultaneous RT–PCR and have investigated correlations between these parameters and the expression of both ER and EGFR mRNA and protein as measured by RT–PCR and ICA and with Ki67 immunostaining. A direct association was found between c-erbB3 and c-erbB4 mRNA and ER marker status measured by either RT–PCR (c-erbB3 P=0.0003; c-erbB4 P=0.02) or ICA (c-erbB-3 P=0.002; c-erbB4 P=0.01). Inverse associations were seen between c-erbB3 and c-erbB4 mRNA marker status and EGFR membrane protein (c-erbB3: P=0.003; c-erbB4: P=0.003) and mRNA (c-erbB4: P=0.009) status. These associations were reinforced by Spearman Rank Correlation Tests. A significant relationship was seen between Ki67 and c-erbB4 mRNA status and level. Measurements of c-erbB3 protein levels in tumour samples removed from a further 89 patients of known response to endocrine therapy: (i) confirmed the relationship between c-erbB3 and ER and (ii) identified that patients whose ER positive tumours expressed high levels of c-erbB3 were most likely to benefit from endocrine measures. A non-significant trend was recorded between c-erbB3 levels and Ki67 immunostaining. These results clearly demonstrate that increased c-erbB3 and c-erbB4 expression appears to be associated with the prognostically-favourable ER phenotype.