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A study of HER2 gene amplification and protein expression in gastric cancer
  1. Benedict Yan1,
  2. Ee Xuan Yau2,
  3. Siti Shyba Bte Omar1,
  4. Chee Wee Ong2,
  5. Brendan Pang1,
  6. Khay Guan Yeoh3,
  7. Manuel Salto-Tellez1,2
  1. 1Department of Pathology, National University Health System and National University of Singapore, Singapore, Republic of Singapore
  2. 2Cancer Science Institute, National University of Singapore, Singapore, Republic of Singapore
  3. 3Department of Medicine, National University Health System and National University of Singapore, Singapore, Republic of Singapore
  1. Correspondence to Manuel Salto-Tellez, Department of Pathology, National University Health System and National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Republic of Singapore; patmst{at}nus.edu.sg

Abstract

Background Gastric cancer is a leading cause of cancer-related mortality, and current treatment outcomes for advanced disease remain poor. HER2 has been identified as a potential candidate for targeted therapy in gastric cancers displaying HER2 gene amplification and protein overexpression.

Aims To study the prevalence rate of HER2 gene amplification/overexpression in a local population, and determine the concordance rate between the various modalities.

Methods 128 gastric cancer samples were analysed by fluorescence (FISH) and chromogenic (CISH) in situ hybridisation and immunohistochemistry (IHC). The relation between HER2 status and various clinicopathological parameters was also analysed.

Results 11.7% (15/128) and 9.4% (12/128) of gastric cancers displayed HER2 gene amplification and protein overexpression (score 3+), respectively, with a perfect correlation between the FISH and CISH analyses. There was also a significant inverse correlation between overall survival and HER2 protein overexpression in intestinal-type gastric carcinomas (p<0.05).

Conclusion Results, besides corroborating existing reports that discrepancies exist between HER2 ISH and IHC assays, also suggest the need to rigorously evaluate CISH as an independent reference standard for assessment of HER2 amplification in gastric cancers.

  • Gastric cancer
  • HER2
  • fluorescence in situ hybridisation (FISH)
  • chromogenic in situ hybridisation
  • immunohistochemistry

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Footnotes

  • BY and YEX contributed equally to this work.

  • Funding MS-T receives funding support from SCS grants MN-05, MN-05R and MN-77, awarded by the Singapore Cancer Syndicate, Agency for Science, Technology and Research, Singapore, Cancer Science Institute of Singapore and the Singapore Gastric Cancer Consortium.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the National University of Singapore Institutional Review Board (NUS-IRB 06-063).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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