Her2 Testing in Gastric Cancer

Key facts

  • HER2 gene amplification and protein over-expression occurs in a significant proportion of gastric cancers
  • HerceptinTM is licensed for the treatment of metastatic and locally advanced gastric cancer and adenocarcinoma of the gastro-oesophageal junction
  • HER2 testing is a pre-requisite for prescribing of HerceptinTM

Over-expression of the membrane-associated receptor protein HER2 (erbB-2), as a consequence of gene amplification, occurs in 7%-27% of gastric cancers.

The EMEA has recently licensed the HER2-targeted antibody trastuzu-mab (HerceptinTM) for the treatment of metastatic and locally advanced gastric cancer and adenocarcinoma of the gastro-oesophageal junction. Patients achieving an IHC score of 3+, or who are 2+ by IHC and HER2-amplified by in situ hybridisation are considered eligible for Herceptin treatment.

Source Bioscience offers the FDA-approved, standardised and validated Ventana PATHWAY™ immunohistochemistry test for HER2 protein expression, coupled with the new Ventana BDISH (Brightfield Dual-Colour In Situ Hybridisation) test for confirming HER2 gene status, both run on the Ventana BenchMark™ XT slide processing system.

Evaluation

Specimens immunostained for HER2 protein are assessed visually by a registered pathologist, with specialised training in the scoring of gastric cancers, who will assign a score of 0 to 3+; a score of 3+ is regarded as positive for HER2 protein over-expression, and indicative of HER2 gene amplification. Scores of 0 and 1+ are considered negative. Specimens achieving a score of 2+ are considered borderline, and are referred for BDISH HER2 gene analysis. BDISH scores are expressed as ratios of HER2 gene copy number to copy number of chromosome 17. A score greater than 2 is considered evidence of HER2 amplification.

Examples of immunostaining for HER2 protein (top), and BDISH detection of the HER2 gene (bottom) in gastric tumours amplified for HER2