HER2 assessment by silver in situ hybridization: where are we now?

HER2 testing in breast and gastric cancer is critical not only as a prognostic tool but also as a predictive marker for response to the humanized monoclonal antibody trastuzumab. Currently, HER2 status is assessed on histological and cytological specimens by conventional validated methods such as immunohistochemistry and FISH, while bright-field in situ hybridization techniques, such as silver in situ hybridization and chromogenic in situ hybridization, may offer performance benefits over FISH. The major points are first, technical issues, advantages and disadvantages relevant to each methods, and their clinical implications and second, the well-known genetic heterogeneity of HER2, and the occurrence of polysomy of chromosome 17. This review aims to summarize the growing body of literature on the accuracy of bright-field in situ techniques, notably silver in situ hybridization, in assessing HER2 status, and to discuss the role of such methods in pathology practice.