Developing a cell line standard for HER2/neu.

Advancements in medical genetics are resulting in the identification of key molecules in the pathways that lead to carcinogenesis. With these discoveries, drugs are developed that target a protein or block a particular molecular pathway with the potential to bring about disease regression. The HER2/neu tyrosine kinase receptor is one such target. Therapy based on the humanised monoclonal antibody, trastuzumab, targets HER-2/neu and inhibits the growth of HER2/neu-overexpressing breast cancer cells. Assays for markers to HER2/neu are forerunners of many more predictive assays that are likely to enter the clinical arena in the near future, many of which will require quantitative analysis. In the field of tissue based assay systems controversies are well documented on the lack of reproducibility in the immunohistochemical analysis HER2/neu. The problems encountered to date lye with the difficulty in reliably standardising the immunohistochemical assay. One of the first steps in addressing this issue is to develop a standard reference material against which the 'variable' of assay sensitivity for HER2/neu can be accurately gauged. Work in the United States and Europe aimed at providing a standard reference material for HER2/neu has already commenced. Preliminary work conducted in Europe shows that development of a standard comprised of cell lines is feasible and when employed as part of an external quality assurance programme, results in significant improvement in the numbers of clinical laboratories achieving appropriate results. In the United States it has been proposed that two standards consisting of well characterized cell lines will be produced, one a National Institute of Standards and Technology (NIST)--certifiable standard, and the other a commercially developed standard for use in all HER2/neu testing. The aim is that this approach will act as a template for other important predictive markers of the future.