Interpretation based on 2018 ASCO/CAP Guidelines
The updated 2018 ASCO/CAP guideline focused on three dual-probe ISH groups (groups 2, 3, and 4) with less common ISH patterns, and recommended routinely associated IHC review for these ISH groups to achieve the most accurate determination of HER2 status. Additionally, in the updated 2018 ASCO/CAP guideline, HER2 status, as determined by ISH, is categorized to positive or negative with no equivocal results.
Interpretation steps:
- Read 20 cells, document the copy number of the HER2 gene (orange) and the copy number of the centromere 17 (CEP17) signal (green).
- Calculate the average copy number of each, per cell.
- Calculate the average ratio of HER2 to centromere 17.
Interpretation results:
- NEGATIVE for amplification:
- HER2/CEP17 ratio <2.0 with average HER2 copy number <4.0 (group 5)
- HER2/CEP17 ratio ≥2.0 and average HER2 copy number <4.0 (group 2) with concurrent IHC 2+
- HER2/CEP17 ratio <2.0 with average HER2 copy number ≥4.0 and <6.0 (group 4) with concurrent IHC 2+
- Groups 2, 3, and 4 with concurrent IHC 0 or 1+
- POSITIVE for amplification:
- HER2/CEP17 ratio ≥2.0 and average HER2 copy number ≥4.0 (group 1)
- HER2/CEP17 ratio ≥2.0 and average HER2 copy number <4.0 (group 2) with concurrent IHC 3+
- HER2/CEP17 ratio <2.0 and average HER2 copy number ≥6.0 (group 3) with concurrent IHC 2+
- HER2/CEP17 ratio <2.0 and average HER2 copy number ≥6.0 (group 3) with concurrent IHC 3+
- HER2/CEP17 ratio <2.0 with average HER2 copy number ≥4.0 and <6.0 (group 4) with concurrent IHC 3+
- EQUIVOCAL (uncertain/ambiguous results): no equivocal category
Journal of Pathology and Translational Medicine 2020; 54: 34-44 HER2 Status in Breast Cancer: Changes in Guidelines and Complicating Factors for Interpretation
jptm-2019-11-03.pdf (nih.gov).
