ASCO GI Coverage: Australian Study Finds ISH to Be the Best Assessor of HER2 Expression in Gastric Cancer

Charles Bankhead
Published: Wednesday, Mar 02, 2011
In situ hybridization (ISH) yields the best results for assessing HER2 expression in gastric cancer, according to a multilaboratory analysis of testing methods. The laboratories demonstrated good concordance for ISH evaluation of 100 tissue specimens from patients with gastric or gastroesophageal junction adenocarcinoma. In contrast, only moderate agreement emerged from immunohistochemistry (IHC) staining, except for IHC 3 specimens, according to M. Priyanthi Kumarasinghe, MBBS, MD, FRCPA, and colleagues.

"The good concordance across laboratories for HER2 copy number suggests that ISH is the optimal method for HER2 testing in gastric cancer," said Kumarasinghe, a clinical pathologist at Queen Elizabeth II Medical Center in Perth, Australia. "The agreement between laboratories on HER2 score of samples by IHC was moderate, likely due to discordance between laboratories on the assignment of IHC 1 and IHC 2 samples, suggesting the need for ISH confirmation in these cases."

Up to one-third of advanced gastric cancers exhibit amplification or overexpression of HER2. Studies have shown that the anti-HER2 monoclonal antibody improves survival in HER2-positive disease, the investigators noted. As part of a national program, HER2 testing in breast cancer has become routine in Australia. However, pathologists have limited experience in the evaluation of HER2 expression in gastric cancer tissue. The accuracy and consistency of testing will have a major role in identifying gastric cancer patients who are candidates for treatment with trastuzumab.

To assess the status of HER2 testing, Kumarasinghe and colleagues conducted an interlaboratory reproducibility study involving 9 reference laboratories in Australia. Each laboratory received a tissue microarray encompassing 100 prescreened samples of gastric adenocarcinoma. The laboratories evaluated the specimens for HER2 expression by IHC and ISH, which comprises chromogenic ISH (CISH), silver ISH (SISH), or fluorescence ISH (FISH).

For all levels of HER2 (IHC 0-3 ) expression, the laboratories had overall agreement of 68%. Grouping IHC 0/1 together resulted in an overall accuracy of 84%, increasing to 92% when IHC 3 was a separate category and the other 3 levels of expression were considered as 1 level.

Laboratories using CISH/ SISH had good or very good concordance when HER2 expression was defined by copy number (? = 0.81), but agreement declined when test results were defined by HER2:chromosome 17 (chr17) ratio (? = 0.69). When results were defined by HER2 copy number (? = 0.90), comparison of central FISH with CISH/SISH showed the best results.

On the basis of their findings, the investigators recommended the following testing algorithm for HER2 expression in gastric cancer:

  •  IHC alone is not sufficient for determining HER2 status in gastric cancer.
  •  IHC should be used for initial evaluation, followed by single-probe ISH evaluation for specimens that exhibit
  •  Use of the HER2/chr17 ratio in ISH should be restricted to equivocal cases.
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Kumarasinghe MP, Morey A, Bilous M, Fox SB, GATHER Study Group. Gastric HER2 testing study (GATHER): Evaluation of gastric cancer testing accuracy in Australia. Paper presented at: 2011 Gastrointestinal Cancers Symposium; January 2011; San Francisco, CA.

Published by Oncology & Biotech News. February 2011.


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