Tissue microarrays for high-throughput molecular pathology.

Abstract

Modern research technologies, including DNA, protein, and antibody microarrays identify a steadily growing number of clues that are useful in molecular disease classification, drug development, and the prediction of response to treatment. Subsequent validation of the clinical importance of such candidate genes or proteins requires large-scale analysis of human tissues. To date, this analysis constitutes an important bottleneck in the process of discovery because tissue analysis by the conventional slide-by-slide strategy is slow and expensive. To overcome these limitations, tissue microarray (TMA) technology has been developed. TMA allows for the simultaneous analysis of up to 1,000 tissue samples in a single experiment, using all types of in-situ analyses including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RNA in situ hybridization (RNA-ISH). TMA technology has the potential to greatly facilitate the translation of basic research into clinical practice. Potential applications include the establishment of associations between molecular changes and clinical endpoints, testing of potential therapeutic targets using tissue samples from specific cancer patients, standardization of molecular detection of targets, and rapid translation of results from cell lines and animal models to human cancer. Because of its beneficial economic aspects and ability to differentiate ethnic differences in tumor biology, TMA applications may become particularly important in developing countries.