From the 2018 American Society of Clinical Oncologists (ASCO) and College of American Pathologists (CAP) guideline recommendations, CISH and FISH scoring criteria:
- HER2 must be reported POSITIVE with ISH based on:
- Single-probe, average HER2 copy number ≥6.0 signals/cell
- Dual-probe HER2/CEP17 ratio ≥2.0 with an average HER2 copy number ≥4.0 signals/cell
- Dual-probe HER2/CEP17 ratio ≥2.0 with an average HER2 copy number <4.0 signals/cell
- definitive diagnosis rendered based on additional Her-2 IHC staining, if not already performed
- Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number ≥6.0 signals/cell
- definitive diagnosis rendered based on additional Her-2 IHC staining, if not already performed
- HER2 must be reported as EQUIVOCAL with ISH based on:
- Single-probe ISH average copy number ≥4.0 and <6.0 signals/cell
- Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number ≥4.0 and <6.0 signals/cell
- definitive diagnosis rendered based on additional Her-2 IHC staining, if not already performed
- HER2 must be reported as NEGATIVE with ISH based on:
- Single-probe average HER2 copy number <4.0 signals/cell
- Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number <4.0 signals/cell
Counting is performed on at least 20 cells. A pathologist must confirm the counting and involve only the invasive component. Comparisons are needed to distinguish between normal breast and tumor cells to manage the interpretation of difficult-to-interpret areas. CISH amplification is defined as >10 discrete copies per nucleus or large gene copy clusters in >50% of nuclei. Unaltered gene copy is 1–5 copies per nucleus (Tanner).
