title: Clinical significance of the quantitative assessment of the cytosolic concentration of HER-2/neu protein in breast cancer by immunoenzymatic assay (ELISA).
abstract: OBJECTIVE
  Retrospective analysis to assess the prognostic and predictive value of HER-2/ neu expression in breast tumors, quantified by enzyme immunoassay (ELISA).
  
  
  METHODS
  Quantification of HER-2/neu was performed on cytosolic extracts from 914 cases of primary invasive breast carcinomas. Relapse-free and overall survival data were available from 889 patients. The prognostic value of HER-2/neu levels was assessed considering them as a continuous, dichotomic or quartile variable.
  
  
  RESULTS
  Cytosolic HER-2/neu levels ranged widely in breast carcinomas (median: 746.5 NHU/mg; range: 2.8-80,000 NHU/mg protein). HER-2/neu protein levels were significantly higher in either moderately or poorly differentiated tumors, as well as in those showing a ductal histological type, aneuploidy or a high S-phase fraction. There was a significant and positive association between cytosolic and membranous HER-2/neu levels (n=162, r sub S=0.53; P<0.0001). In addition, cytosolic HER-2/neu level correlated weakly with progesterone receptors but not with estrogen receptors. Elevated cytosolic HER-2/neu levels (> or =1,400 NHU/mg protein) were associated with a high probability of both shortened relapse-free survival and overall survival. This same cut-off value was obtained when we divided the overall group of patients in a training set. However, this HER-2/neu value did not achieve any statistical significance in a validation set used to make sure that the cut-off was correct. Nevertheless, when we divided the obtained data into three different groups with respect to the quartile values (Q) of the intratumoral oncoprotein levels (< or = Q1 vs Q1-Q2 vs > Q3), we observed that patients with either low HER-2/ neu levels (< or = Q1) or high HER-2/neu levels (> Q3) had shorter both relapse-free survival and overall survival curves than those patients with intermediate HER-2/neu levels. On the other hand, high HER-2/neu levels predicted a poor response to adjuvant chemotherapy but not to adjuvant hormonal therapy with tamoxifen.
  
  
  CONCLUSIONS
  The results of the present investigation indicate that by quantitatively determining the content of HER-2/neu oncoprotein, groups of high-risk breast cancer patients could be identified, for a more effective clinical management.
authors.affiliation: Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Corte
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rodil
authors.forename: Julio
authors.initials: J
authors.lastname: Vázquez
authors.forename: Lucia
authors.initials: L
authors.lastname: García
authors.forename: Juan C
authors.initials: JC
authors.lastname: Rodríguez
authors.forename: Miguel
authors.initials: M
authors.lastname: Bongera
authors.forename: José C
authors.initials: JC
authors.lastname: Fernández
authors.forename: Luis O
authors.initials: LO
authors.lastname: González
authors.forename: Ma Luz
authors.initials: ML
authors.lastname: Lamelas
authors.forename: Maite
authors.initials: M
authors.lastname: Allende
authors.forename: José L
authors.initials: JL
authors.lastname: García-Muñiz
authors.forename: Antonio
authors.initials: A
authors.lastname: Fueyo
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Vizoso
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000188:drug therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000175:diagnosis* / Q000188:drug therapy; D003600:Cytosol / Q000737:chemistry; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D016019:Survival Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases