Article Text

PDF
Dual-colour HER2/Chromosome 17 chromogenic in situ hybridisation assay enables accurate assessment of HER2 genomic status in gastric cancer and has potential utility in HER2 testing of biopsy samples
  1. Benedict Yan1,
  2. Ee Xuan Yau2,
  3. Shoa Nian Choo1,
  4. Chee Wee Ong2,
  5. Kol Jia Yong2,
  6. Brendan Pang1,
  7. Manuel Salto-Tellez2,3
  1. 1Department of Pathology, National University Health System and National University of Singapore, Singapore
  2. 2Cancer Science Institute, National University of Singapore, Singapore
  3. 3Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK
  1. Correspondence to Professor Dr Manuel Salto-Tellez, CCRCB, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; m.salto-tellez{at}qub.ac.uk

Abstract

Background Determination of HER2 protein expression by immunohistochemistry (IHC) and genomic status by fluorescent in situ hybridisation (FISH) are important in identifying a subset of high HER2-expressing gastric cancers that might respond to trastuzumab. Although FISH is considered the standard for determination of HER2 genomic status, brightfield ISH is being increasingly recognised as a viable alternative. Also, the impact of HER2 protein expression/genomic heterogeneity on the accuracy of HER2 testing has not been well studied in the context of gastric biopsy samples.

Aims/methods To study the utility of brightfield ISH in the evaluation of HER2 genomic status, the correlation coefficient between dual-colour HER2/Chromosome 17 chromogenic in situ hybridisation (CISH) and FISH was ascertained. To study the impact of intratumoral heterogeneity on the accuracy of HER2 testing, the concordance rate of HER2 protein expression/genomic status between matched biopsies and surgical resection specimens of high HER2-expressing gastric cancers was ascertained.

Results The dual-colour CISH assay showed a 100% concordance rate with FISH results in 119 samples (Pearson correlation coefficient 0.987, p<0.001). Five of the 11 high-HER2 expressors (defined as IHC 3+ or IHC 2+/FISH-amplified according to Trastuzumab for Gastric Cancer trial criteria) showed an IHC 3+ score on matched biopsies (concordance rate 45.5%). Nine of these 11 cases showed HER2 amplification on matched biopsies (concordance rate 81.8%).

Conclusion Dual-colour CISH is an excellent alternative for the evaluation of HER2 genomic status in gastric cancers. Determination of HER2 status by HER2 IHC alone in limited gastric biopsy samples results in a high false-negative rate, and diagnostic accuracy appears to be improved if HER2 genomic testing, either alone or concurrently with IHC, is performed for HER2 testing.

  • Gastric cancer
  • HER2
  • fluorescent in situ hybridisation
  • brightfield
  • dual-colour
  • chromogenic in situ hybridisation
  • molecular pathology
  • molecular oncology
  • cancer research
  • gastrointestinal disease
  • molecular genetics
  • colon
  • haematopathology

Statistics from Altmetric.com

Footnotes

  • Competing interests MS-T is a member of the Key Opinion Leaders Group of Ventana-Roche.

  • Ethics approval Ethics approval was obtained from the relevant Institutional Review Board.

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

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.