The most commonly used, rapid, and cost-effective means to assess HER2 status is protein over-expression using IHC. Patients with tumors that are 3+ by IHC are good candidates for treatment with Herceptin® (trastuzumab). However, studies have established that gene amplification results provide a better prognostic correlation with response to trastuzumab. A small subset of patients with tumors having 2+ IHC results was found to show no reaction to the drug, whereas all those having gene amplification responded favorably.
HER2 gene amplification is primarily detected by in situ hybridization and traditionally by FISH methods, which use fluorescence to detect the signals. Unfortunately, the FISH method is both cumbersome and expensive. It requires a fluorescent microscope, appropriate filters, and a sophisticated camera, making it a poor screening tool.
Chromogenic in situ hybridization (CISH) has advantages over FISH because it can be assessed with an ordinary light microscope and costs one-quarter the cost of FISH. CISH can potentially detect HER2 gene amplification and minimize, if not eliminate, the subjectivity risk with IHC interpretation.
