How Tissue Microarrays Yield Gene Expression Profiles

Tissue microarray technology is not only very powerful, but extremely useful in the medical field. The technology yields gene expression profiles that are a door to oncology, tumor biology, and diagnostic test development. A microarray is defined as a grid of DNA segments of known sequence that is used to test and map DNA fragments, antibodies, or proteins. Tissue microarrays consist of paraffin blocks in which up to 1000 separate tissue cores are assembled in array fashion to allow multiplex histological analysis.

The genesis of the tissue microarray (TMA) technology two decades ago was the discovery in 1986 by Battifora et al of how 1 mm thick rods of different tissues could be wrapped in a sausage-like sheet of small intestine and embedded in paraffin to form a multitumor tissue block. In 1987, the technique was refined as an array. The inability to pinpoint the nature of each tissue specimen remained problematic, although simultaneous assessments of many tissue specimens at the same time under the same conditions was now feasible. By 1998, Kononen et al had further refined TMA to permit rapid construction of microarrays and commercialization of the TMA device. The popularity of the TMA device continues to increase with commercial marketing.

The potentials of TMA are that various tissue types can be rotated and embedded so as to be sure that the tissue of interest is present in the sample, and that TMAs permit efficient and cost-effective analysis of numerous samples by IHC, FISH, and other histochemistry assays.

The downfalls are that each tissue core included in the microarray may represent only a small fraction of the lesion and may not fully represent or predict tumor biology, and that TMAs should not be used in tumors which usually exhibit marked tissue heterogeneity

Also, a TMA with 30 cases may be sufficient for quality control, but it will not be adequate for biomarker analyses.

TMAs are now playing, and will continue to play, a key role in various therapeutic areas including tumor biology and oncology. Probably the most important being the role in supporting the targeted therapies for cancer. The targeted therapies in oncology work on the specific parts of cells such as genes, enzymes, receptors, that make cancer cells different from healthy cells. The expectation is that TMA will be a tool to promote the rapid translation of basic research into the clinical setting.


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