c-erb-b2 Amplification Test, GE Junction Cancer
1. A pathology report is required in order for testing to be performed.
2. A reason for testing much be provided.
3. The pathology report must include the type of fixation used as well as the time of fixation.
The HER2 FISH test is not approved by the FDA for this indication and should be used as an adjunct to existing clinical and pathologic information.
The assay has been optimized for formalin-fixed, paraffin-embedded tissue specimens. Optimal fixation should be between 6 and 72 hours in 10% neutral buffered formalin.
The prognostic information provided by the HER2 status of a patient's tumor should not be interpreted in isolation because other prognostic features (eg, lymph node status, tumor size) may be of equal or greater importance in determining the patient's prognosis.
Gastroesophageal cancer is one of the most commonly diagnosed cancers. To date, chemotherapy for gastroesophageal cancer is often ineffective and its prognosis remains poor. Recent studies suggest that the HER2 oncogene can be used as a marker to identify aggressive disease.
In much the same way as was demonstrated for HER2-positive breast cancer, the HER2 gene status in gastroesophageal cancers can be used to determine treatment approaches. Amplification of the HER2 gene and overexpression of the human epidermal growth factor receptor 2 (HER2) protein have been associated with a shorter disease-free survival and shorter overall survival in gastric and gastroesophageal junction cancers. Patients whose tumors demonstrate HER2 amplification or overexpression may be candidates for treatment with the drugs that target the HER2 protein or its downstream pathways (eg, trastuzumab [Herceptin], pertuzumab).
An interpretive report will be provided. Results are interpreted utilizing the 2016 College of American Pathologists (CAP)/American Society for Clinical Pathology (ASCP)/American Society of Clinical Oncology (ASCO) guidelines for gastric tumors, and the guidelines used by the Traztuzumab for Gastric Cancer (ToGA) trial.
Specimens with equivocal results as defined by 2016 CAP/ASCP/ASCO guidelines will not have reflex testing performed using an alternative FISH probe set. The report will include a complete interpretation including the HER2:D17Z1 results.
The degree of HER2 amplification varies in tumors. Some exhibit high levels of amplification (HER2:D17Z1 ratio >4.0), whereas others exhibit low-level amplification (HER2:D17Z1 ratio of 2.0-4.0). It is not currently known if patients with different levels of amplification have the same prognosis or response to therapy.
Reports also interpret the HER2 copy number changes relative to chromosome 17 copy number (aneusomy) or potential structural genomic abnormalities that increase HER2 copy number.
Rare cases may not show HER2 amplification but still have human epidermal growth factor receptor 2 (HER2) protein overexpression demonstrated by immunohistochemistry. The clinical significance of HER2 protein overexpression in the absence of HER2 gene amplification is unclear. However, these patients may have a worse prognosis and be candidates for treatments that target the HER2 protein or its downstream pathways.