Dako’s HER2 Testing FAQ on ASCO and CAP Guidelines
Dako welcomes the ASCO and CAP organizations’ interest in improving the uniformity of HER2 testing. To support the guidelines, Dako has written answers for frequently asked questions (FAQs) to aid laboratories in their performance requirements for HER2 testing. Below are some questions and answers to aid you in your pursuit of quality test results.
Recently, ASCO and CAP published their updated guidelines for HER2 testing (1, 2).
The guidelines emphasize the importance of the use of validated HER2 tests in breast cancer patient HER2 assessment. Since the launch in 1998 of HercepTest™ validated for assessment of HER2 protein overexpression, Dako has provided accurate and consistent HER2 testing in human breast tissue specimens. With the addition of Dako’s HER2 FISH pharmDx™ Kit validated for assessment of HER2 gene amplification and its Automated Cellular Imaging System (ACIS III) enhancing patient assessment through improved interobserver reproducibility, Dako continuously seeks to assist pathology laboratories in improving their quality of HER2 testing.
The aim of the guideline is to improve the robustness of the HER2 tests. ASCO has highlighted the lack of concordance between general pathology laboratory and central laboratory test results seen during clinical trials. The updated HER2 guidelines are very supportive for the use of validated assays for determination of HER2 gene amplification and HER2 protein overexpression.
The updated guidelines differ in some situations from protocols and scoring guidelines included in the package inserts of the FDA-approved products. The information currently stated in the package inserts for HercepTest™ (3) and HER2 FISH pharmDx™ (4) as well as in the HercepTest™ Interpretation Manual (5) is the approved wording by regulatory agencies.
The major areas differing from the approved protocols and scoring guidelines addressed in the articles are:
- Laboratories performing HER2 testing will be required to validate the laboratory results either by documenting concordance between IHC and FISH results, or by achieving concordance with another laboratory that tests duplicate breast cancer specimens. When IHC and FISH concordance is performed, it is required that there are:
- 95% concordance for negative cases (IHC 0 and 1+ and FISH-).
- 95% for 3+ IHC and FISH+.
- If this level of concordance cannot be reached, technical performance of the test should be reviewed.
- All IHC 2+ cases are categorized as equivocal and should be reflexed to FISH testing.
- Implementation of an updated definition of 3+ HER2 protein overexpression requiring a minimum of 30% of tumor cells staining at 3+ intensity.
- Mandatory participation in Quality Assurance Programs for HER2 testing, if the laboratory plans to continue to offer HER2 testing.
- Specimens must be fixed in 10% buffered formalin (NBF) (6-48 h).
For a more complete overview of the suggested guidelines, please refer to Table 4 in the referenced articles in the publication from ASCO and CAP.