As HER2 can function as both homodimer and heterodimer with other ERbB/EGFR receptors to activate downstream signaling cascades leading to tumorigenesis, assessment for HER2 overexpression/amplification is recommended in both GEA and BTC.1-3 However, HER2 assessment may be underutilized; a cross-sectional study of 6,032 patients with advanced GEA of whom 1007 were HER2-positive found that compared with patients diagnosed with de novo metastatic disease, those with early-stage GEA and who (a) did not undergo surgery or (b) had recurrence of the disease, were less likely to receive timely HER2 testing and anti-HER2 therapy with trastuzumab. The study concluded that despite guideline recommendations, HER2 testing and anti-HER2 treatment remain underused.4
There are some challenges associated with HER2 testing in GEAs and these must be addressed for accuracy in determining HER2 overexpression/amplification.
Some challenges associated with HER2 testing in BTCs can include:
For both GEA and BTC, HER2 is assessed by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) assays. Both techniques can utilize formalin-fixed or paraffin-embedded biopsy tissue or surgical specimens and cytological samples. Only equivocal cases are subjected to FISH due to the higher time and cost involved. Additionally, for GEA, hybridization probes directed toward HER2 and chromosome enumeration probe 17 (CEP17) are used and a positive result is when the HER2/CEP17 ratio is ≥2.
Next-generation sequencing (NGS) is typically used when there is an inadequate amount of diagnostic tissue or inability to complete a traditional biopsy for IHC/FISH, as well as when multiple genomic variations need to be simultaneously detected.1-3,8 These three techniques, based on specimen availability and clinical context, can support effective clinical decision making.8
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