title: The significance of the HER-2 status in esophageal adenocarcinoma for survival: an immunohistochemical and an in situ hybridization study.
abstract: BACKGROUND
  In esophageal adenocarcinoma (EAC), concordance and prognostic significance of human epidermal growth factor 2 (HER-2) protein overexpression and gene amplification are equivocal, which led us to reevaluate this by immunohistochemistry (IHC) and in situ hybridization.
  
  
  METHODS
  One hundred and fifty-four patients were included in a tissue micro array (TMA). HER-2 gene amplification was assessed by fluorescence and silver-enhanced in situ hybridization (FISH and SISH) and expression with the HercepTest™.
  
  
  RESULTS
  HER-2 was amplified in 16% by SISH and 18% by FISH. HER-2 positivity (IHC 3+ or 2+ with ISH+) was seen in 12% and overexpression (IHC 2+/3+) in 14%. Concordance was 92% between SISH/IHC, 90% between FISH/IHC and 95% between SISH/FISH. All IHC 3+ cases were amplified by SISH and in 93% by FISH. Of the IHC 2+cases, this was 33% (SISH) and 50% (FISH). Of the IHC 1+ cases, still 6% (SISH) and 8% (FISH) showed amplification. HER-2 positivity, overexpression and amplification were all associated with poor cancer-specific survival, in univariate analysis. Furthermore, HER-2 positivity and amplification (SISH) were independently associated with poor survival (hazard ratio, HR 6.343; 95% CI 1.218-36.234; P = 0.029 and HR 3.231; 95% CI 1.092-9.563; P = 0.034).
  
  
  CONCLUSIONS
  HER-2 positivity and gene amplification are fairly frequent and independently associated with poor survival.
authors: Department of Surgery, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
authors: M J D
authors: MJ
authors: Prins
authors: J P
authors: JP
authors: Ruurda
authors: P J
authors: PJ
authors: van Diest
authors: R
authors: R
authors: van Hillegersberg
authors: F J W
authors: FJ
authors: Ten Kate
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human