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HER-2/neu Gene Amplification in Esophageal Adenocarcinoma and Its Influence on Survival

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

HER-2/neu (c-erbB-2, HER2) gene amplification and protein overexpression have been associated with poor prognosis in several solid tumors, including breast and gastric cancer. Its incidence and significance in esophageal adenocarcinoma is unknown.

Materials and Methods

Tissue microarrays were successfully constructed from 89 paraffin-embedded archival specimens of esophageal adenocarcinomas for HER2 gene amplification by silver-enhanced in situ hybridization (SISH). No patients had undergone neoadjuvant therapy. Protein overexpression was tested with immunohistochemistry (IHC) using automated immunostaining (Ventana Benchmark). Incidence of HER2 positivity, correlation to clinicopathological variables in esophageal cancer patients, and concordance between SISH and IHC were determined.

Results

True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression. No significant associations were found among gene amplification and clinicopathological factors. The 5-year survival rates were 57% for esophageal cancer patients with HER2 amplification compared with 32% without, but the difference in overall survival was not significant (P = .37). The correlation between SISH and IHC was statistically significant (P < .0001).

Conclusion

While molecular targeting may be possible for approximately 16% of esophageal adenocarcinoma patients, HER2 oncogene amplification did not influence survival in this study.

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Acknowledgment

This work was funded by a 2008 Research Grant from the Society of American Gastroenterologists and Surgeons (SAGES). We would like to thank Professor Glyn Jamieson for his constructive comments regarding the manuscript. We also appreciate the efforts of Carolyn Lally, Lorelle Smith, Janet Pinno, and Nicky Ascott in managing the Royal Adelaide Hospital Esophageal Cancer database.

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Authors and Affiliations

  1. Discipline of Surgery, University of Adelaide, Adelaide, SA, Australia

    Sarah K. Thompson MD, FRCSC

  2. Discipline of Public Health, University of Adelaide, Adelaide, SA, Australia

    Thomas R. Sullivan BMa&CompSc(Hons)

  3. Division of Tissue Pathology, SA Pathology, Adelaide, SA, Australia

    Ruth Davies BMedSc & Andrew R. Ruszkiewicz MD, FRCPA

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  1. Sarah K. Thompson MD, FRCSC
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  2. Thomas R. Sullivan BMa&CompSc(Hons)
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  3. Ruth Davies BMedSc
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  4. Andrew R. Ruszkiewicz MD, FRCPA
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Correspondence to Sarah K. Thompson MD, FRCSC.

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Thompson, S.K., Sullivan, T.R., Davies, R. et al. HER-2/neu Gene Amplification in Esophageal Adenocarcinoma and Its Influence on Survival. Ann Surg Oncol 18, 2010–2017 (2011). https://doi.org/10.1245/s10434-011-1554-1

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  • DOI: https://doi.org/10.1245/s10434-011-1554-1

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