Introduction to An Evolving Diagnostic and Research Tool
The recent advances in the study of human molecular genetics have shown that mechanisms involved in gene-based disease can be crucial. Studies are now using large numbers of clinical specimens in the research of new diagnostic and prognostic markers to help translate the new discoveries from basic sciences to application in clinical practice. New molecular biology techniques have played an important role in the understanding of the progression and pathogenesis of diseases such as cancer. The basic understanding of molecular mechanisms in the progression of normal tissues to tumors that are malignant is key in understanding the mechanism of cancers. This can lead to improvements of detection, treatment and cures fir diseases such as cancers. Clinical tissue studies have found several novel markers that are at the gene level. The authentication of these markers using the standard histopathological techniques can consume a lot of time, costly, and labor intensive especially when several different markers are being tested on a variety of specimens.
Tissue microarray is a recent method that has been used in the field of pathology that can overcome these challenges. It was a method that was designed to help researchers with high throughput molecular biology techniques that enables hem to assess the expression if disease related genes or gene products that can be seen simultaneously on a large number of tissue samples. Parallel molecular profiling is also made possible at the protein, RNA, and DNA level. Tissue microarray technique allows the pathologist to perform an analysis such as immunohistochemistry, fluorescence in situ hybridization (FISH) or RNA in situ hybridization on a large scale. Advantages include that these analyses can be performed substantially faster and is more cost efficient compared to other conventional approaches. The spots that represent a unique cloned cDNA or oligonucleotide is much larger and contain small histologic sections in tissue microarrays.
The tissue microarray technique is becoming increasingly popular although it is relatively new. It was first introduced by Battifora 20 years ago where a “sausage block” method involved wrapping 1mm thick rods which was then paraffin embedded, sections cut, and examined. By 1987, the array format was conceived by Wan and colleagues. While the tissue microarray technique has a significant advantage where multiple tissues could be simultaneously examined under identical conditions, individual rods were unable to be satisfactorily identified which leads to limited meaningful interpretation. In 1998, Kononen et al addressed these limitations and invented a device that could rapidly and accurately construct tissue microarrays that are easily accessible to almost all pathology labs. This invention has led to a dramatic increase in utilization and popularity of the technique.
The Tissue Microarray Technique
The tissue microarray technique is able to organize small amounts of biological specimens on a solid support. By extracting cylindrical core biopsies of tissues from paraffin blocks, these are re-embedded into one single microarray block. The donor blocks are first obtained and sectioned to produce standard slides that can be then stained with hematoxylin and eosin. A pathologist is then required to examine the slides, so the area of interest can be marked. As technology progresses, the technique can now support as many as more than 2000 sections per slide. Through this method, an entire cohort of cases can be analyzed through the staining of one or two master slides instead of hundreds.
The Advantages and Applications of Tissue Microarrays
Compared to standard techniques, there are may advantages of the tissue microarray technique. some of it include:
a) Amplification of a scarce resource
Since a standard histological section is approximately 3 to5mm thick, after it has been used for primary diagnosis, the archived block can still yield material for about 100 assays. Once optimized for microarray construction, it can be needle biopsied 200 to 300 times or more. Therefore, instead of 50 to 100 conventional sections, the microarray technique can yield enough material for 500,000 assays which essentially amplifies the limited tissue resource.
b) Simultaneous analysis of specimens
Through the high throughput data acquisition, the tissue microarray technique allows the simultaneous analysis of large numbers of specimens at the same time which leads to cost efficiency, less time consumption, and uniformity of results.
c) Experimental uniformity
Since all samples are treated identically, including staining, processing techniques, and environmental factors, tissue microarray technique allows the analysis of an entire cohort simultaneously. This standardizes variables such as antigen retrieval, incubation times, temperature, and more.
There are many more advantages of the tissue microarray technique and it has proven to be and efficient and effective tool for quality assurance programs. It facilitates standardization, can be used in internal quality control, and optimization of diagnostic reagents. It helps facilitate translation new discoveries to clinical applications.it has many uses and has a range of potential applications in research and drug discovery. It will not be surprising if the technique will become widely used for all types of research.
Jawhar NMT. Tissue microarray: a rapidly evolving diagnostic and research tool. Ann Saudi Med. 2009; 29(2):123-127