C-ERBB3 AND C-ERBB4 EXPRESSION IS A FEATURE OF THE ENDOCRINE RESPONSIVE PHENOTYPE IN CLINICAL BREAST-CANCER

We examined c-erbB3 and c-erbB4 mRNA expression in 47 primary breast c ancer samples by simultaneous RT-PCR and have investigated correlation s between these parameters and the expression of both ER and EGFR mRNA and protein as measured by RT-PCR and ICA and with Ki67 immunostainin g, 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-erb B4 P = 0.02) or ICA (c-erbB-3 P = 0.002; c-erbB4 P = 0.01). Inverse as sociations were seen between c-erbB3 and c-erbB4 mRNA marker status an d EGFR membrane protein (c-erbB3: P = 0.003; c-erbB4: P = 0.003) and m RNA (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-erbB 3 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 pos itive tumours expressed high levels of c-erbB3 were most likely to ben efit from endocrine measures. A non-significant trend was recorded bet ween c-erbB3 levels and Ki67 immunostaining, These results clearly dem onstrate that increased c-erbB3 and c-erbB4 expression appears to be a ssociated with the prognostically-favourable ER phenotype.