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; cerbB4: P=0.003) and mRNA (c-erbB4: P=0.009) status. These associations were reinforced by Spearman Rank Correlation Tests. A signi®cant 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) con®rmed the relationship between c-erbB3 and ER and (ii) identi®ed that patients whose ER positive tumours expressed high levels of c-erbB3 were most likely to bene®t from endocrine measures. A non-signi®cant 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.

The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients

“…This suggests that expression of HER1 and HER2 is involved in tumour progression and poor prognosis in the bladder tumours only when HER3 and HER4 are low. In keeping with our results, studies on breast cancer investigating the expression of the individual EGF receptors also show that increased HER3 and HER4 expression appears to be associated with better prognosis (Quinn et al, 1994;Knowlden et al, 1998). However, it should be noted that in another study, only HER4 was found to be associated with a better prognosis whereas HER1, HER2 and HER3 overexpression was associated with a poor outcome (Witton et al, 2003).…”

“…Epidermal growth factor family gene expression can reliably be studied at the mRNA level and based on a number of studies, the expression is likely to reflect the presence of the corresponding protein (Knowlden et al, 1998;Walker and Dearing, 1999;Suo et al, 2002;Junttila et al, 2003).…”

Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

“…The mRNA expression levels of HER3 and HER4 receptors were positively correlated to each other and negatively correlated to EGFR, in complete agreement with previously reported data (Knowlden et al, 1998;Pawlowski et al, 2000;Bieche et al, 2003). In addition, we demonstrated a positive association between HER2 and HER3 mRNA expression.…”

The ERBB3 receptor in cancer and cancer gene therapy

“…38 On the other hand, for mRNAs, a positive relationship between ERBB3 and ER was noted, along with increased benefit of expression of both with regard to endocrine therapy. 202 Similarly ERBB3 mRNA expression in 38 mammary cancers was associated with ER positivity and correlated with ERα mRNA as well as with estrogen-related receptor α mRNA. 196 It has been suggested 195 that these discrepancies may be explained in part by the presence of soluble, inhibitory sERBB3.…”