title: Quantification of HER2 autoantibodies in the amplification phenomenon of HER2 in breast cancer.
abstract: BACKGROUND
  Gene amplification of HER2 (human epidermal growth factor receptor 2) is a well-known phenomenon in various cancers. However, little is known about the mechanism of the gene amplification phenomenon itself. Autoantibodies to cellular receptors have been described in several cancer types. We hypothesised that autoantibodies against HER2 might have a stimulatory capacity and could be the cause of the HER2 gene amplification phenomenon. To investigate this, we developed a test for the detection of autoantibodies against HER2 in serum (S-HER2Ab).
  
  
  METHODS
  Blood and tissue samples were collected from 311 women consecutively admitted for surgical treatment of primary breast cancer. Paraffin embedded tissue sections were analysed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 protein concentrations in tissue were determined in 115 patients. Circulating extracellular domain of HER2 (S-HER2) was measured using the Advia Centaur (Siemens AG, Munich, Germany). Analysis for autoantibodies was developed on an ImmunoCAP 100 (Phadia AB, Uppsala, Sweden) with an automated Fluorescent Enzyme Immuno Assay.
  
  
  RESULTS
  Of 311 women, 55 (17.7%) had HER2Ab and 51 (16.4%) showed amplification of the HER2 gene determined by IHC/FISH. Eleven women had detectable S-HER2Ab as well as HER2 gene amplification, but no statistically significant correlation was found between the two phenomena. A significantly higher level of S-HER2Ab was found both in HER2 gene-amplified and non-amplified breast cancer patients compared to an age-matched healthy control group. No statistically significant difference in presence or concentration of S-HER2Ab was found in HER2 gene-amplified vs. non-amplified breast cancer.
  
  
  CONCLUSIONS
  S-HER2Ab can be measured accurately with the ImmunoCAP 100. There is an increased prevalence and concentration of S-HER2Ab in breast cancer patients but no correlation with HER2 gene amplification. We conclude that autoantibodies against HER2 do not seem to be the cause of HER2 gene amplification.
authors.affiliation: Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. jejala@dadlnet.dk
authors.forename: Jens-Jacob L
authors.initials: JJ
authors.lastname: Lauterlein
authors.forename: Eva R B
authors.initials: ER
authors.lastname: Petersen
authors.forename: Dorte Aa
authors.initials: DA
authors.lastname: Olsen
authors.forename: Birthe
authors.initials: B
authors.lastname: Østergaard
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005784:Gene Amplification; D006801:Humans; D057230:Limit of Detection; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000235:genetics* / Q000276:immunology; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D001323:Autoantibodies; D018719:Erb-b2 Receptor Tyrosine Kinases