Understanding the specific characteristics of a tumor is important for effective cancer treatment. One such characteristic, particularly relevant in breast and gastric cancers, involves the HER2 protein. Determining a tumor’s HER2 status helps medical professionals tailor a personalized treatment plan, aiming for the most beneficial outcomes.
Understanding HER2 and Its Role
HER2, or Human Epidermal growth factor Receptor 2, is a protein found on the surface of all human cells. It regulates cell growth, division, and repair by functioning as a receptor that receives signals for cell multiplication. Healthy cells typically have two copies of the HER2 gene, producing a normal amount of HER2 protein.
However, in some cancers, the HER2 gene undergoes amplification, leading to excessive production of HER2 proteins on the cell surface (overexpression). This abundance of HER2 protein continuously signals cancer cells to grow and divide aggressively. HER2 overexpression is observed in approximately 15-30% of breast cancers and 10-30% of gastric cancers. Identifying this overexpression indicates potential responsiveness to specific HER2-blocking treatments.
The FISH Testing Method
To detect HER2 gene amplification, a specialized laboratory technique called Fluorescence In Situ Hybridization (FISH) is often used. FISH is a precise method that visualizes and counts HER2 gene copies within cancer cells. The process begins with a tissue sample, obtained from a biopsy, which is then prepared on a slide.
Fluorescent probes are introduced to the sample; they hybridize to the HER2 gene and a control gene, typically on chromosome 17 (CEP17). Once bound, these probes fluoresce under a special microscope, allowing pathologists to count HER2 gene signals and compare them to control gene signals. FISH is a reliable method for assessing HER2 gene amplification due to its direct gene-level analysis. It is often performed when initial screening tests, such as immunohistochemistry (IHC), yield inconclusive or equivocal results.
Deciphering HER2 FISH Results
Interpreting HER2 FISH results involves calculating a ratio: the number of HER2 gene copies divided by the number of control gene copies (HER2/CEP17 ratio). This ratio determines the tumor’s HER2 status. Results fall into three main categories.
A HER2 negative result typically indicates a HER2/CEP17 ratio less than 2.0, with a low average HER2 gene copy number. Conversely, a HER2 positive result signifies HER2 gene amplification, defined by a HER2/CEP17 ratio of 2.0 or greater. Some guidelines also consider a high absolute HER2 copy number, even if the ratio is below 2.0, as HER2 positive.
Sometimes, results are classified as equivocal or borderline. This occurs when the HER2/CEP17 ratio or average HER2 gene copy number falls into an ambiguous range. Equivocal results often necessitate further review, such as re-testing or additional analyses, to ensure accurate classification and guide treatment decisions.
How Results Guide Cancer Care
HER2 FISH results directly influence a patient’s cancer treatment strategy. For HER2-positive cancers, these results indicate likely responsiveness to specific HER2-targeted therapies. These therapies block HER2 protein activity or deliver cytotoxic agents directly to HER2-overexpressing cells. Common targeted therapies include monoclonal antibodies like trastuzumab and pertuzumab, which inhibit HER2 signaling, and antibody-drug conjugates such as trastuzumab deruxtecan, which combine a targeted antibody with a chemotherapy drug. These treatments have significantly improved outcomes for patients with HER2-positive cancers.
For HER2-negative cancers, HER2-targeted therapies are ineffective, as they do not rely on HER2 overexpression for growth. Other treatment approaches include chemotherapy, hormone therapy (if hormone receptor-positive), or immunotherapy. HER2 status also provides prognostic insights. Historically, HER2-positive cancers were more aggressive, but targeted therapies have considerably improved their prognosis.