HER-2 diagnostics in breast cancer:: Current methods and future perspectives

The transmembrane HER-2 receptor is 185 kD of molecular weight and is encoded by the proto oncogene HER-2 on the long arm of chromosome 17 (17q 12-21). Over-expression of HER-2 is found in about one third of all breast carcinomas. Determining the HER-2 status is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin(TM)) in the therapy of metastatic breast cancer. Various test assays for HER-2 either on the protein level (immunhistochemistry [IHC], enzyme-linked immunosorbent assay [ELISA], western blot) or on the gene level (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], polymerase chain reaction [PCR], and southern blot) are available. However, IHC and FISH are most often applied. For routine HER-2 testing a combination of both methods is recommended. IHC should be used for screening, followed by FISH only in those cases scored as 2+ by the HercepTest. In future, CISH may represent a useful alternative to FISH. In CISH fluorescent dyes are replaced by chromogenes, facilitating the use of light microscopes and the filing of slides. Quantitative analysis of the shed extracellular domain of HER-2 (HER-2 ECD) in the patients' serum by ELISA is helpful for clinical use. With HER-2 ECD as a surrogate marker of the tumor volume monitoring of adjuvant therapies and tumor recurrence would be feasible. However, more prospective studies with higher numbers of patients are required for validation of these new methods.