Historically, when the words tissue microarray have been mentioned it was considered as a “research only" tool, but in today’s lab that couldn’t be further from the truth! The Tissue Microarray (TMA) has become an important and integral tool in the ever growing histology laboratory, if utilized and planned correctly.
The TMA was designed as a solution for the limited availability and expense of diagnostic reagents, and limited patient sample size. The initial multi-tissue block, referred to as a sausage, was first introduced by H. Battifora in 1986 and modified in 1990 to the checkerboard tissue block we see today. In 1998, J. Kononen and collaborators developed the current technique using the novel sampling approach of producing regular size and shape cores. This allowed tissues to be more densely and precisely arrayed.
So, what does one use a TMA block for? They can be used for controls and test slides in: histochemical stains, immunohistochemistry (IHC), immunofluorescence (IF), RNAScope or the new Spatial techniques such as GeoMax and MIBI to name a few. The TMA can also be used for new protein discovery, control slides for staining, validation slides and a way to get the most out of a spatial experiment.
The key to a good TMA is in the initial design. You need to really think about the purpose for the TMA and design it accordingly. When planning a TMA ask yourself these four questions: 1) Is this for control purposes or will it be the actual test samples? 2) Can we incorporate controls within the sample set? 3) What size core do we need? 4) Will this be a screening block for new antibodies, used on a specific panel?
For example: lymphoid for CD markers, specific for lymphomas- a specific type cancer, maybe for general screening of a novel protein to characterize the staining patterns in multiple tissues. Maybe you want to do larger cores, make one from cell blocks, or you could even design and implement using frozen tissue. There are so many ways you can design this tool. The more thorough you are in planning the better the result.
The TMA can be done manually, semi-automated to fully automated. For all practical purposes, unless you are planning on making TMA’s for clinical trials or pharmaceutical studies, the semi–automated or manual methods will serve your purpose well and these methods are more cost effective and flexible.
Finding a source of tissues for TMA construction is often the most difficult part. For human samples, we work with a pathologist to aid us in the quality of samples chosen, patient information to fit criteria and our Tissue Procurement Facility (TPF) to collect what we need. Working with a TPF is a great way to collect patient material. They have already done the job of consenting the patients, material is de-ID'ed and the blocks can either be purchased or a small core can be taken and the block returned so others can also access the material. In doing animal research the material needs to be in compliance with the animal regulations for your facility. These blocks are often easier to obtain and have a lot more tissue to work with. Once you have your samples and a map designed, construction can begin! The time needed to construct the TMA will depend on core size, quality of the donor blocks and what method you are using.
So, why a TMA? Standardization, conservation of precious tissue, easy to use, and the TMA is great for validation or high throughput testing. The method can offer technology that allows technologists and pathologists to evaluate numerous tissues at one time on a single slide. Depending on core size, a wide range of tissue samples can be assembled in a single block. With this tool you can look at disease progression, prognostic values, prevalence, and experimental options. The TMA can provide associations between tumor genotype and phenotype. Honestly, the options and uses are endless. The once research only tool has become an option available to any size facility for a multitude of uses.
Go ahead, try one! For more information about TMAs join me for my Learning Lab at the 2023 NSH Convention, Tissue Microarray 101: The Basics, on September 9.
Written By: Colleen Forster, BS, HT (ASCP), QIHC (ASCP)
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