The significance of the HER-2 status in esophageal adenocarcinoma for survival: An immunohistochemical and an in situ hybridization study

M. J.D. Prins, J. P. Ruurda, P. J. van diest, R. van Hillegersberg, F. J.W. ten kate

Research output: Contribution to journalArticlepeer-review

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 Hercep Test™. 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). Conclusion: HER-2 positivity and gene amplification are fairly frequent and independently associated with poor survival.

Original languageEnglish (US)
Article numbermds640
Pages (from-to)1290-1297
Number of pages8
JournalAnnals of Oncology
Volume24
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • Esophageal adenocarcinoma
  • Gene amplification
  • HER-2
  • Protein

ASJC Scopus subject areas

  • Hematology
  • Oncology

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