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