Approximately 10-34% of human invasive breast carcinomas (in ductal carcinoma in situ, DCIS) have increased levels of a protein called HER-2/neu on the cancer's cell surface. Detection of either the HER-2/neu gene or gene product, i.e. protein, can be used to determine the patient's prognosis and to choose potential therapies, such as chemotherapy and the antibody based therapy, HerceptinTM, which is directed against the HER-2/neu protein.
There have been many research techniques used to detect both the HER-2/neu gene and protein, but for the medical consumer it is important to review the current commercially available and FDA (Food and Drug Administration) approved HER-2/neu diagnostic tests. The three tests available are:
1) HercepTest (DAKO Corporation, Caprenteria,CA), FDA approved for Herceptin eligibility. 2) Inform (Ventana Medical Systems, Inc., Tucson, AZ) , FDA approved for predicting disease prognosis. 3)Pathvysion (Vysis, Downers Grove, IL), FDA approved for Taxotere response.
The tests are technically divided into two different categories. HercepTest detects the overexpression of the HER-2/neu protein by immunohistochemical (IHC) staining methods, while Inform and Pathvysion detect the HER-2/neu gene.
IHC staining, which has been the predominant diagnostic method, uses either archival fixed paraffin-embedded tissue, fresh or flash-frozen tissue. Antibodies first stick to the HER-2/neu protein in the various tissue samples and are then visualized with a peroxidase stain. In a flash frozen sample, the tissue is subject to liquid nitrogen temperatures (-150 C). In contrast to the one-step flash freezing process used for preserving frozen tissue samples, in the tissue archival process, the tissue sample is fixed, processed, and embedded into paraffin. The amount of fixing time, method of processing, and temperature of paraffin embedding can all vary. Although a fresh or frozen tissue sample that is IHC stained will give the most accurate results because the tissue is not treated with any chemicals when used fresh or is less likely to be degraded during the one step flash freezing process, the archival fixed paraffin-embedded tissue samples are more frequently used because they are more widely available and only a small tissue sample is required for preservation.
The two gene based tests, Inform and Pathvysion, which use fluorescent in situ hybridization (FISH), are newer methods of testing for the HER-2/neu cellular alteration. A fluorescent probe, which is targeted to the HER-2/neu gene, will light up the gene if it is present in the cells of the tissue sample. Like the IHC staining method, the FISH method requires very little sample, is performed on a single tissue section, and assesses the specimen on a cell specific basis. When one compares the accuracy of the IHC and FISH detection methods, the FISH method is 96.5% as accurate as the IHC method. It is important to note that 10-12% of breast cancer tumors, which overexpress the HER-2/neu protein, do not express the HER-2/neu gene and the overexpression of the HER-2/neu protein is thought to be clinically relevant.
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