Introduction to Tissue Microarray
The recent advance in technology resulted in the progression of fields such as human molecular genetics. Through this development, gene-based mechanisms have been revealed in many areas of medicine. One of the most important step is to translate the new findings from basic science and apply it to clinical practice. This can be done through the study of prognostic and diagnostic markers using large numbers of specimens. Utilizing new molecular biology techniques, the understanding of pathogenesis and progression of disease has increased tremendously. However, the authentication of these markers using standard techniques can be very time consuming, labor intensive, and costly.
Tissue Microarray
Tissue microarray (TMA) is a fairly new technique that has been developed and can be used to overcome these significant problems. It was developed and designed as a high-throughput method to allow researchers to assess expression of disease related genes or gene products in a large number of samples simultaneously. In other words, TMA allows researchers to perform a large-scale analysis at a shorter time and lower costs. First reported 20 years ago by Battifora, TMA was described as a sausage block method where rods of different tissues were embedded in a paraffin block which was then cut and examined. In 1998, Kononen et al invented a device that could rapidly and accurately construct TMAs making it accessible to almost all pathology labs. This led to the dramatic increase and utilization of the technique.
As briefly mentioned, TMAs are composite paraffin blocks that are constructed through the extraction of cylindrical core biopsies from donor blocks which are then re-embedded into a single microarray block. The following is a general idea of the steps for TMA.
Donor blocks that are retrieved are sectioned into standard microscopic slides and stained with hematoxylin and eosin.
The slides are then examined by an experienced pathologist to mark the area of interest and samples are then arrayed.
A tissue core is acquired from the donor block using a TMA instrument.
The core is placed into an empty paraffin block at a specific coordinate.
The sampling process can be repeated to produce a large number of samples which are placed into the recipient block, known as the final TMA block.
Sections are cut from the TMA block generating slides for molecular and immunohistochemical analysis.
TMA allows the analysis of entire cohorts by staining one or two master array slides instead of the conventional way of staining hundreds of standard slides.
Advantages and Applications of TMAs
TMAs have many advantages such as:
Amplification: Samples for analysis can be maximized as TMAs yield more material for analysis which amplifies the limited tissue resource.
Efficient: TMAs allow simultaneous analysis of large numbers of samples.
Uniformity: Through this technique, all tissue samples are treated identically and are amenable to many methods such as histochemical stains, immunologic stains, in situ hybridization, and more. Since the entire cohort can be analyzed in one batch, TMA standardizes the whole batch by eliminating variables such as antigen retrieval, temperature, incubation time, and more.
Cost: A small amount of reagent and very few personnel are needed to perform the experiment making the method to be cost efficient.
Tissue conservation: The sample block that is used can be cored several times without destroying the original block.
Some of the applications of TMA include:
Assessment of quality assurance programs through the standardization of variables, internal quality control, and optimization of diagnostic reagents.
Facilitation of translation of molecular discoveries to clinical applications such as tumor research, profiling of tumors, validation of histopathological specimens, and more. It also allows the assessment of tumor progression, prognosis, and patient outcome.
Limitations and Disadvantages
Currently, TMA still has room for improvement such as increasing control over sampling depth, enhancing quality of needles, array designs, bettering sectioning and transferring techniques, staining techniques, less annual operation, and upgrading precision in automation. The TMA technology should also be digitalized as digital image analysis that scans the TMAs in virtual slides allows it to be analyzed algorithmically. This improvement may accelerate the discovery of new biomarkers. One of the main disadvantages of TMA technology are the facilities that can be quite expensive. Due to the high cost of array machines, its use in general practice is limited in many countries. Many laboratories in developing countries may not be able to afford such technology as a manual TMA machine costs approximately USD $1200 while an automated one can cost from USD $12,000 to USD $42,000. Many researchers are currently trying to devise more cost effective TMA construction techniques.
Conclusion
TMAs have proven to be effective and efficient in the field of molecular genetics. In high throughput molecular analysis, the technique helps in the identification of new diagnostic and prognostic markers in human tumors. It has a wide range of applications in research, prognostic oncology, and pharmacology. It is now one of the most widely used tool for all tissue-based research and has led to a rapid acceleration in the transition of research findings into clinical application.
