title: 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 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.
authors.affiliation: Tenovus Cancer Research Centre, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Knowlden
authors.forename: J M
authors.initials: JM
authors.lastname: Gee
authors.forename: L T
authors.initials: LT
authors.lastname: Seery
authors.forename: L
authors.initials: L
authors.lastname: Farrow
authors.forename: W J
authors.initials: WJ
authors.lastname: Gullick
authors.forename: I O
authors.initials: IO
authors.lastname: Ellis
authors.forename: R W
authors.initials: RW
authors.lastname: Blamey
authors.forename: J F
authors.initials: JF
authors.lastname: Robertson
authors.forename: R I
authors.initials: RI
authors.lastname: Nicholson
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D010641:Phenotype; D017698:Postmenopause; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D013629:Tamoxifen; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4