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.

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 using TMAs. Further, the authors mentioned a study in which clinco-pathological associations were made in TMAs, but not in large sections, which further strengthens the position of TMAs as a powerful research tool.

In order to fully exploit TMAs and to maximize the chances of a successful study outcome, proper consideration must be given to the array source. While some researchers construct their own slides, this requires a high level of technical expertise and resources. Construction requires tissue acquisition and pathological review, as well as preparation of the slides. Because of the expertise and time needed, considerable savings can be realized by using commercially available slides. However, there are some points to consider when evaluating potential suppliers.

  1. In most of the laboratories, adhesive coated tape is used for sectioning the tissue array. However, trace amounts of adhesive material remains in the slides and can interfere with subsequent immunohistochemistry staining.
  2. While the ability to study decades old archived tissue is a major advantage of TMAs, sectioning and storage of the tissue is important. Slides should be stored and packaged in an anoxic state and ideally are not sectioned until the slides are ordered.
  3. While not always necessary, the availability of matched samples, that is diseased andnormal samples from the same organ and patient, can provide comparison data which maybe helpful in evaluating molecular aberrations or correlating data about the presence or absence of specific targets within the same individual.

Despite the apparent simplicity of TMA technology, it clearly holds promise for many different areas of research—especially in the field of cancer research. Undoubtedly, as costs associated with bringing new pharmaceutical therapeutics to market increase, as well as the continued focus of rational drug design and development, TMAs may well become a standard pre-clinical investigation tool.

IMGENEX Histo-Array™ Tissue Microarrays

IMGENEX Histo-Array™ tissue array slides are a simple, powerful, inexpensive, yet highly efficient method for expression analysis or localization studies of molecular targets at the DNA, RNA or protein level. Over ninety different human or animal tissue array slides are available, with tissue samples densities ranging from 24 to 146 spots per slide, corresponding to tissue sample sizes of 4mm to 1mm. Slides are available with different cancerous, normal, normal adjacent, or diseased tissues of different organs as well as matched tissue samples for certain slides (when noted). Each slide includes patient data on all tissue samples including age, sex, diagnosis, and any applicable staging codes. Each Histo-Array™ tissue array slide is freshly cut, coated with paraffin, and packaged under anoxic conditions when you order. This ensures maximum freshness and minimal antigen loss. Additionally, while many laboratories use adhesive tape for sectioning tissue arrays, our slides are constructed without the use of adhesive tape. This ensures that no trace amounts of adhesive will remain on the tissues which could interfere with IHC staining and protects antigen integrity.

Tissues mounted to standard silanized slides
> Formalin-fixed paraffin-embedded human tissues
> 24-146 tissue samples per slide (4mm to 1mm diameter spots), 4 um thick
> Ready to use for immunohistochemistry, in situ hybridization, FISH and in situ PCR
> Variety of cancerous and normal tissues, many organs available
> Mouse, rat, and cell line arrays also available

> Fresh-- TMAs aren’t cut until ordered
> Paraffin coated, inert gas packaging for maximal shelf life
> Adhesive-free sectioning
> Serial sections available
> Rigorous quality control
> Significant savings of time and reagent usage
> High-throughput or manual processing and analysis
> Patient data included
> TNM staged samples

List of antibodies validated for IHC
Download our 38 page color Tissue Array booklet. This comprehensive reference tool includes H&E images of all slides, multiple protocols, tissue data, s well as a complete tissue index to quickly determine the right slide for you.







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