title: Serum HER2 supports HER2-testing in tissue at the time of primary diagnosis of breast cancer.
abstract: OBJECTIVE
  HER2 in tissue is of high prognostic value. Soluble HER2, the extracellular domain (ECD), has been suggested to be a helpful biomarker. We investigated whether there is a relationship between HER2 ECD and HER2 in tissue and whether this relationship could be used for diagnostic purposes.
  
  
  METHODS
  HER2 ECD was measured in healthy individuals (N=283, 184 females, 99 males), in patients with history of breast cancer (BC) with no evidence of disease (N=249) as well as in BC patients before any treatment (N=565). HER2 in tissue was determined by immunohistochemistry and HER2 ECD was analyzed by immunoassay.
  
  
  RESULTS
  HER2 ECD levels were higher in healthy men than in healthy women (medians 12.9 ng/mL vs. 9.9 ng/mL, p<0.001). We observed an age dependency in women that means the older the women the higher the HER2 ECD level. In treated BC patients there was only a weak difference between younger and older women. For patients without distant metastases as well as patients with metastatic disease we observed a correlation of HER2 in serum and tissue. The median concentrations of HER2 ECD were 11.7 ng/mL (13.2 ng/mL) for the HER2-negative (HER2-positive) patients in the non-metastatic-group (p<0.001) and 11.9 ng/mL (16.0 ng/mL) in the metastatic-group (p=0.01). Using a cut-off of 30 ng/mL the HER2 in tissue was always positive, corresponding to a specificity of 99.8% and a sensitivity of 10.3%.
  
  
  CONCLUSIONS
  There is a strong correlation between HER2 ECD and HER2 in tissue. HER2 ECD supports the HER2 testing in tissue and may reveal false-negative tissue findings.
authors.affiliation: Medical Department III, Klinikum Großhadern, University Hospital, Munich, Germany. Electronic address: Dorit.DiGioia@med.uni-muenchen.de.
authors.forename: Dorit
authors.initials: D
authors.lastname: Di Gioia
authors.affiliation: Institute of Clinical Chemistry, Klinikum Großhadern, University Hospital, Munich, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Dresse
authors.affiliation: Institute of Pathology, Klinikum Großhadern, University Hospital, Munich, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.affiliation: Institute of Clinical Chemistry, Klinikum Großhadern, University Hospital, Munich, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.affiliation: Medical Department III, Klinikum Großhadern, University Hospital, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.affiliation: Gynecological Department, Klinikum Großhadern, University Hospital, Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Kahlert
authors.affiliation: Institute of Clinical Chemistry, Klinikum Großhadern, University Hospital, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D006801:Humans; D007120:Immunochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000097:blood*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast cancer; HER2 ECD; HER2/neu; Healthy individuals; Shed antigen