Tissue Microarrays And Archival Surgical Material

Human tissue specimens are among the most valuable resources that biomedical researchers can use in their efforts to reach a molecular understanding of the malignant process which might ultimately translate into improvements in the treatment and survival of cancer patients. At the same time, the tissue that has been removed from a patient during a therapeutic intervention remains essential to that patient's care. In an effort to balance these competing needs of tissue-based medical research and also preserve the samples for essential patient care, new tools have been developed for performing research on patients' surgical material. This handout is prepared to inform pathology departments and patients on the details of this new tool - tissue microarray - and how it is may be used to facilitate biomedical research.

Traditional approaches to laboratory research employing human surgical material have involved either the use of tissue sections on microscope slides, or obtaining the entire paraffin embedded block for research purposes. Both approaches have benefits and drawbacks. Further, these methods are not completely satisfactory for many research questions. Recently, a new method, - tissue microarray ("TMA") - was created and overcomes some of the challenges..

What is a TMA?

A TMA is a paraffin block into which cores from tens to hundreds of donor blocks have been inserted (see Figure 1). The recipient block, the TMA, is then sectioned to produce slides, each of which contains a disc of tissue from each of original cores, permitting all the tissue samples on a single slide to be analyzed simultaneously (see Figure 2).

How are the tissue cores obtained from the donor paraffin block?

First an H&E slide from the block is reviewed, and marked to define where the tissue of interest is. The slide is then used as a template to target the tissue. Small needles are used to bore a core of tissue from the block. Depending on the project, anywhere from 1 to 5 cores may be removed from a single block. At no time is all of the diagnostic material from the block removed.

What happens to the block after the cores are removed?

After the core are removed, the donor block is returned to the institution from which it had been borrowed. If the need arises, new H&E sections can be made directly from the block, just as would be done under ordinary circumstances. No special manipulation of the block is required. The tiny holes created by removal of the tissue cores do not need to be refilled with paraffin.

Why are multiple cores sometimes taken?

Multiple cores may be taken to examine specific sub-populations of cells that are present within the block. More typically, additional cores are taken to permit construction of additional TMA blocks. This approach conserves substantially more tissue in the donor block than would be possible if the donor block were subjected to multiple standard recuts in an effort to acquire sufficient material for research purposes. A typical surgical block can be sectioned into ~ 200 to 300 slides; in the course of so doing, the block would be exhausted. However, a single core from that same block can contribute to a TMA block from which 150 to 300 slides can be made; this process leaves the donor block almost completely intact. If an additional core is placed in a second TMA block, the same number of additional slides can be made. Thus, two cores from a single block can produce twice the amount of research material that could be obtained by consuming an entire block through standard sectioning! As an added benefit, the donor block can be returned to its archive for future diagnostic use.

Are the cores of tissue really representative?

Yes, and no. There are some tumor systems and studies, where they are not representative. In some instances, 3 cores are required. For some studies of blood vessels in tumors, TMAs can not be used. We make every effort to match the goals of the research with the maximum conservation of tissue.

What are the TMAs used for when they are constructed?

The majority of TMA slides are used for immunohistochemical staining. The slides are used in laboratory-based research projects aimed at developing better diagnostic markers, better prognostic markers, as well as critical data regarding the molecular origins of the disease being studied

Are TMAs used in clinical medicine?

Currently, TMAs are used as control slides in some laboratories. They are frequently used for immunohistochemical control slides.

Where can I learn more about TMAs?

Our website (www.cancer.gov/tarp) has additional information describing this new technology, and also provides links to others who use TMAs in their research studies.

If you have additional questions related to the technical aspects of TMA, please do not hesitate to contact:

Dr. Stephen M. Hewitt, MD, PhD, FCAP
Chief, Tissue Array Research Program
Laboratory of Pathology,
National Cancer Institute,
National Institutes of Health
Bethesda, MD
phone: 301-496-0040
email: genejock@helix.nih.gov
web: www.cancer.gov/tarp