title: The complete family of epidermal growth factor receptors and their ligands are co-ordinately expressed in breast cancer.
abstract: The levels of expression of the four receptors and eleven ligands composing the epidermal growth factor family were measured using immunohistochemical staining in one hundred cases of breast cancer. All of the family were expressed to some degree in some cases; however, individual cases showed a very wide range of expression of the family from essentially none to all the factors at high levels. The highest aggregate level of expression of a receptor was HER2 followed by HER1, then HER3, then HER4. The ligands (including two splice variants of the NRG1 and NRG2 genes) broadly fell into three groups, those with the highest aggregate expression were Epigen, Epiregulin, Neuregulin 1alpha, Neuregulin 2alpha, Neuregulin 2beta, Neuregulin 4 and TGFalpha, moderate expression was seen with EGF, Neuregulin 1beta and Neuregulin 3, and relatively low levels of expression were seen of HB-EGF, Betacellulin and Amphiregulin. Statistical analysis using Spearman's Rank Correlation showed a positive correlation of expression between each of the factors. Analysing the data using the Cox Proportional Hazards model showed that, in this dataset, the most powerful predictors of relapse free interval and overall survival were the combined measurement of only Epigen and Neuregulin 4.
authors.affiliation: Computing Laboratory, University of Kent, Canterbury, Kent CT1 7NJ, UK.
authors.forename: Emmet
authors.initials: E
authors.lastname: McIntyre
authors.forename: Edith
authors.initials: E
authors.lastname: Blackburn
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Brown
authors.forename: Colin G
authors.initials: CG
authors.lastname: Johnson
authors.forename: William J
authors.initials: WJ
authors.lastname: Gullick
mesh_terms: D066258:Amphiregulin; D066259:Betacellulin; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000235:genetics; D066261:Epigen; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018815:Genes, erbB; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D008024:Ligands; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D020880:Neuregulins / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D020893:Receptor, ErbB-3 / Q000096:biosynthesis; D066247:Receptor, ErbB-4; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D066258:Amphiregulin; D066259:Betacellulin; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor; D066261:Epigen; D066246:ErbB Receptors; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D009363:Neoplasm Proteins; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D017978:Receptors, Growth Factor; D016211:Transforming Growth Factor alpha; C587848:AREG protein, human; C587851:BTC protein, human; C587854:EPGN protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C587689:ERBB4 protein, human