Tissue microarrays for miniaturized high-throughput molecular profiling of tumors.

New high-throughput screening technologies such as complementary (cDNA) microarrays allow identification of hundreds of candidate genes in one experiment. To prioritize the leads obtained in such studies, it is necessary to analyze a large number of tissues for candidate gene expression. Tissue microarray (TMA) technology greatly facilitates such analyses. In this method, hundreds of minute tissue samples (0.6-mm diameter) can be placed on one microscope glass slide. The TMA approach allows simultaneous analysis of all tissues with in situ methods (immunohistochemistry, fluorescence in situ hybridization, RNA in situ hybridization) of all tumors in one experiment under highly standardized conditions. TMAs are not restricted to solid tumors but can be manufactured from a variety of other sources, including cell lines, xenografts, and hematologic tissues. In addition to tumor type-specific applications that comprise large numbers of one particular tumor type with extensive histopathologic and clinical data, TMAs are well suited for large-scale molecular epidemiologic studies. For example, genes of interest can be analyzed in multitissue TMAs containing a variety of different human normal tissues and tumor entities. Once tumor types are identified, where a given molecular alteration plays a role, the clinical significance of this molecular alteration can be investigated on tumor-specific TMAs. Thus, TMA technology allows miniaturized high-throughput molecular epidemiologic studies. The TMA technique will markedly accelerate the transition from basic research to clinical applications.