Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation enables accurate assessment of HER2 genomic status in ovarian tumours

J Clin Pathol. 2011 Dec;64(12):1097-101. doi: 10.1136/jclinpath-2011-200082. Epub 2011 Sep 6.

Abstract

Background: Ovarian cancer is a leading cause of gynaecological cancer-related morbidity and mortality. There has been increasing interest in the potential utility of anti-human epidermal growth factor receptor 2 (anti-HER2) agents in the treatment of this disease, with the attendant need to identify suitable predictive biomarkers of response to treatment.

Aims/methods: The authors studied the prevalence of HER2 genomic amplification and overexpression in 85 ovarian tumours in the local patient cohort of this study, as well as the concordance rate between immunohistochemistry, fluorescent in situ hybridisation (FISH) and a dual-colour HER2/chromosome 17 centromere chromogenic in situ hybridisation (CISH) assay.

Results: The authors identified HER2 genomic amplification and protein overexpression in 35.3% (6/17) and 29.4% (5/17), respectively, of primary ovarian mucinous carcinomas. No other cancer subtypes displayed HER2 amplification or protein overexpression. The authors also found a perfect concordance between FISH and dual-colour CISH analysis (κ coefficient 1.0, p<0.001).

Conclusion: The results of this study support existing reports that HER2 genomic amplification and protein overexpression are predominantly found in primary ovarian mucinous carcinomas. Given the perfect concordance between the FISH and dual-colour CISH assays and the advantages of CISH over FISH analysis, future clinical trials investigating the use of anti-HER2 therapeutics in ovarian carcinomas should incorporate dual-colour CISH as part of the HER2 status assessment algorithm.

Publication types

  • Evaluation Study

MeSH terms

  • Adenocarcinoma, Mucinous / genetics*
  • Chromosomes, Human, Pair 17 / genetics*
  • Cohort Studies
  • Color
  • Female
  • Gene Amplification / genetics
  • Genes, erbB-2 / genetics*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization / methods*
  • Ovarian Neoplasms / genetics*
  • Receptor, ErbB-2 / metabolism*
  • Sensitivity and Specificity

Substances

  • Receptor, ErbB-2