Evaluation of the HER2 amplification status in oesophageal adenocarcinoma by conventional and automated FISH: A tissue microarray study

M. J D Prins, J. P. Ruurda, P. J. Van Diest, Richard Van Hillegersberg, F. J W Ten Kate

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The manual fluorescence in situ hybridisation (FISH) Human Epidermal Growth Factor Receptor 2 (HER2)/CEP17 testing method is frequently used, however, it is time consuming and liable to subjectivity. Automation of FISH might increase the throughput and accuracy. Aim: To evaluate the agreement between automated and conventional FISH with regard to a reference test silver-enhanced in situ hybridization (SISH) for HER2 amplification, as well as its prognostic significance. Material and methods: 154 oesophageal adenocarcinomas were included in a tissue microarray. HER2/CEP17 gene amplification was assessed by automated FISH and was compared with conventional HER2/CEP17 testing methods. Results: 46.8% of patients showed HER2 amplified tumours by automated FISH (ratio ≥1.8) compared with 18.1% by conventional FISH. A high automated HER2/CEP17 ratio (≥1.8) was significantly associated with worse survival (HR 1.731; 95% CI 1.075 to 2.786; p=0.024). However, agreement between automated and conventional FISH was only 72.2% and 71.4% between automated FISH and SISH, compared with 94.6% for conventional FISH/SISH. Therefore, thresholds for HER2/CEP17 amplification were sequentially raised from HER2/CEP17 ratio 1.8 till 5.0. A HER2/CEP17 ratio threshold of ≥3.6 had similar prognostic significance as conventional FISH (HR 1.880; 95% CI 1.060 to 3.332; p=0.031 vs HR 1.828; 95% CI 1.102 to 3.033; p=0.020), yielded comparable amplification rates as conventional FISH (14.3% vs 18.1%) and comparable agreement to SISH/Immunohistochemistry (IHC). Conclusions: Automation of HER2 FISH analysis in oesophageal cancer has not been performed before. Automated HER2 is feasible, but it seems that the HER2/CEP17 threshold should be adjusted to ≥3.6 to arrive at best comparability with other methods and prognostic value.

Original languageEnglish (US)
Pages (from-to)26-32
Number of pages7
JournalJournal of Clinical Pathology
Volume67
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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