Introduction
Since the first appearance of tissue microarrays (TMA) more than 18 years ago, usage of TMAs by researchers from a wide range of disciplines has grown tremendously. By arraying different tumor types from multiple tissues on a single slide—oreven arraying with normal tissues, one can analyze a molecular target under highly controlled conditions. Because tissue samples are arrayed on the same slide, tissue morphology can be evaluated using H&E and stained with multiple antibodies specific to different molecular targets. Because of the format, TMAs are amenable to evaluation and analysis by way of either high-throughput automation or manual analysis using standard bright-field microscopy techniques.

Advantages
First described in published research by J. Kononen et al. (Nature Medicine Vol 4. No. 7, 1998 pp. 844-847), TMAs represent a significant advancement in molecular pathology over traditional methods, as they provide the ability to rapidly identify and characterize molecular targets in hundreds or thousands of tissue samples. TMAs are not constrained by technique or application, as slides can be probed using any assay protocol developed for whole tissue sections in a non-destructive manner. Thus, slides can be used for histology, immunochemistry, and FISH. Moreover, because of its miniaturization, an experiment using TMAs can be used to provide information on molecular and protein characteristics such as the incidence of molecular variations in tumor cells, cellular localization, or the detection and development of new prognostic or predictive indicators.

Given the high costs and extended time frames associated with bringing new drugs to market, these benefits make TMAs an ideal tool for primary evaluation of drug targets, as correlating gene and protein expression data in normal and diseased tissue samples can be obtained in a high-throughput manner. Additionally, the data can provide information crucial for rating and prioritizing molecular targets associated with particular clinical outcomes, thus helping to focus drug development efforts.

Dispelling the Myth
A common concern in the use of TMAs is related to the ability of a small tissue core to accurately reflect data about large tumor specimens. It should be evident that a 1.0-2.0mm tissue sample will not uniformly reveal all data from tumors. This is especially true of tumors which can be highly heterogeneous. However, it must be noted that there is an essential difference with respect to the applications of TMAs and their low density counterparts. While generally desirable to use large tissue sections for the purpose of clinical diagnosis,the strength of the TMA lies not in its usage for diagnostics, but as a research tool with the ability to provide statistically significant, population-level data faster and more economically then other methodologies.

Another common concern questions the concordance of TMA data with clinically significant findings obtained from large sections. According to C. Camozzi et al, (Genetic Engineering News Vol 24, No. 20, 2004 pp. 30-42), several studies demonstrating clinical and molecular associations between ER, PR, p53, and HER2 with breast cancer, bladder cancer, and kidney cancer have been confirmed us