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Understanding Tissue Issues
(Biospecimen) Donation

Factors Affecting Tissue Quality

The conditions under which tumor tissue is collected, fixed, preserved, and stored is also an ongoing focus of research, since donated tissue is an invaluable resource.

The life cycle of tissue

All tissue taken from the bodyundergoes a series of steps that must be standardized, documented, and carried out accurately to ensure that the tissue is useable for research. We will discuss each of these steps below.

Collection
Processing
Storage
Analysis

The image below demonstrates these steps:


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Collection

This term refers to how tissue is obtained from an individual. At the collection stage, there are multiple factors that can affect the biomarkers present in your tissue. Called pre-analytes, these factors may affect the tissue before it is processed, stored, or analyzed.


		One study that sought to evaluate the frequency and nature of mistakes made in a laboratory found that pre-analytic mistakes constituted 68% of all errors.
Image provided by CISN archives. All rights reserved.

Some examples of pre-analytic factors include the use of anesthesia during surgery. The compounds used for anesthesia can infiltrate the blood supply and tumor tissue and affect its composition.

Clamping of the veins and arteries during surgery represents another pre-analytic factor. Clamping to reduce bleeding deprives the tumor of its blood supply, thus altering the quality and attributes of the tissue, and has the potential to affect the biomarkers that will be measured in the tissue. The presence of specific biomarkers and the ability to measure such markers effectively is important because it may suggest whether specific treatments are right for a particular patient.

Successful tissue retrieval requires the surgeon’s hand-off to knowledgeable personnel who can handle the tissue appropriately. A trained responsible individual must transport the tissue from the operating room to the lab where it will be preserved.

Processing

Once the tissue is collected from the body, the next step is called processing.


		This refers to the handling of the tissue to prepare it for testing or storage.
Image provided by CISN archives. All rights reserved.

Laboratory technicians must be available in a timely manner to preserve the tissue or otherwise handle it for clinical or research purposes. Temperature, time, and the fixative used all play a crucial role in proper processing.

For example, it is important to consider the temperature of the lab in which the tissue is held while awaiting preservation; the temperature of the storage facility; the effects of freezing and thawing, including multiple instances of freezing and thawing the same sample; the amount of time spent in fixative; and the time spent in storage, since long-term storage can lead to degradation of the sample.

The optimal conditions for tissue collection, processing, and storage will depend on the tissue type, the assays that need to be performed, and whether the tissue will be used for a clinical (diagnostics and treatment) or a research application.

Storage

Tissue is often stored in large facilities called biobanks that may be located within hospitals, research centers, or private facilities.


		Though research units that store biospecimens may differ, at a minimum, they include some form of cryogenic (freezing) facility for tissues that must be kept frozen and a shelving and identification retrieval system.
Image provided by CISN archives. All rights reserved.

Some units may also be linked to data sources that provide information about the variables to be studied (type of disease, outcome, treatment received, individual characteristics).

In its “Best Practices for Biospecimen Storage,” the National Cancer Institute calls for:

standardized protocols for storage, depending on the tissue type extracted (e.g., wet tissue, frozen tissue, paraffin-embedded tissue, blood, serum, urine) and the biomolecules to be analyzed (e.g., RNA, DNA, proteins, lipids).
security warnings that will monitor the function of the storage equipment and alert personnel to any power failures limiting biobank access to specific individuals who are knowledgeable about privacy procedures.

The guidelines, which are extensive, are located at:
http://biospecimens.cancer.gov/bestpractices/2011-NCIBestPractices.pdf

Analysis

Tissue testing or analysis also needs to be standardized to enable accurate comparison of results.

Advances in genetic sequencing and molecular analytic technologies have increased the call for high-quality biospecimens. Some analyses can be performed with minute amounts of tissue. Tests that previously could only be performed with fresh tissue can now be conducted with paraffin-embedded tissue.

As shown in this slide from the National Human Genome Research Institute, the cost of DNA sequencing has dropped significantly since the mapping of the human genome.

The analysis of each biospecimen generates an enormous amount of data. This type of research also requires numerous specimens to note trends in patient cases.

Daniel MacArthur, a UK-based geneticist who writes about “consumer genomics” and blogs at genomesunzipped.org, noted in the February 21, 2011 issue of Wired Magazine, “Our ability to create genetic data is rapidly out-stripping our ability to store and analyze it.”

Following is a discussion of additional hurdles that must be overcome on the path to personalized medicine.

The importance of standardization

Both clinical and tissue research needs to be standardized at all the stages listed above. Many groups and agencies are involved in working to achieve this.

The National Cancer Institute (NCI)’s Office of Biorepositories and Biospecimen Research has noted that, “The lack of standardized, high-quality biospecimens has been widely recognized as one of the most significant roadblocks to the progress of cancer research.”

The NCI has also conducted a review of the state of its funded biospecimen resources and the quality of biospecimens used in cancer research. This review resulted in a document entitled, “NCI Best Practices for Biospecimen Research.” Comprehensive in scope, it identifies technical, operational, ethical, legal, and policy best practices to “ensure a level of consistency and standardization across biospecimen resources.”

For more information, please visit the following websites:

“Content Developed September 1, 2012”