From the Guidelines
For gastric cancer, HER-2 amplification by FISH testing is considered positive when the HER-2/CEP17 ratio is ≥2.0, as this is the standard threshold used to determine if a patient's gastric cancer has HER-2 gene amplification, as supported by the most recent guidelines 1. This threshold is crucial in identifying patients who may benefit from targeted therapies such as trastuzumab (Herceptin). The testing methodology involves fluorescence in situ hybridization (FISH) which directly measures the number of HER-2 gene copies relative to chromosome 17 centromere (CEP17).
- The ratio of HER2 to CEP17 signals helps distinguish true gene amplification from chromosome polysomy.
- For borderline cases, additional cells may need to be counted or immunohistochemistry (IHC) testing may be used as a complementary method to confirm HER-2 status.
- It is also important to note that some guidelines consider cases with a ratio <2.0 but with an average HER-2 copy number ≥6.0 signals per cell as positive, as seen in the ToGA trial 1.
- The clinical importance of HER-2 testing lies in its ability to identify patients who may benefit from targeted therapies, and the testing methodology has been refined over time to ensure accurate results, with recommendations for section thickness, scoring, and interpretation of results 1.
From the Research
HER-2 Amplification in Gastric Cancer
- The level of HER-2 amplification considered positive in gastric cancer using Fluorescence In Situ Hybridization (FISH) testing is typically defined as an HER2/CEP17 ratio ≥ 2.0 2, 3, 4, 5.
- This ratio indicates the number of HER2 gene copies relative to the number of centromere 17 (CEP17) copies, with a ratio of 2.0 or higher suggesting HER2 gene amplification 3.
- However, cases with a CEP17 count ≥ 3.0, also known as "polysomy 17", may require additional evaluation using techniques such as Multiplex Ligation-dependent Probe Amplification (MLPA) to distinguish between true polysomy and centromeric amplification 4.
- The optimal cutoff for the HER2/CEP17 ratio to predict longer overall survival in patients with HER2-positive advanced gastric cancer has been reported to be around 4.48 5.
- Additionally, an HER2/CEP17 ratio of more than 3.69 and an HER2 gene copy number of more than 7.75 have been identified as positive predictive factors for better outcomes with trastuzumab-based chemotherapy in patients with HER2-positive advanced gastric cancer 5.