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Biospecimen Issues:
For Researchers

Overview

To conduct correlative science studies, biospecimen samples are needed. These samples are donated by patients and are taken from tumor tissue, cheek (also called buccal) swabs, blood serum, plasma, needle biopsies or urine. These samples need to be obtained from both cancer patients and healthy people so that comparison research can be conducted.

The emergence of regulations for establishing, maintaining and using biobanks (places to store biospecimens) is forcing issues concerning sample collection, storage, processing and ethical considerations to the forefront.

Unfortunately, the vast majority of the millions of biospecimens in collections around the world are not suitable for making the type of apples-to-apples comparisons that modern cancer biology research demands.

The reason samples are unsuitable is simple, there are no standards for:

  • How surgeons collect tissue samples
  • How pathologists prepare (process) those biospecimens
  • How biobanks store their collected biospecimens
  • How biobanks distribute samples
  • How researchers analyze the samples

Given the exquisite sensitivity of today's analytical techniques, it is nearly impossible to distinguish between molecular fingerprints that are related to cancer and those created by the way a given biospecimen was handled.

As mentioned previously, in order to correct this problem, the National Cancer Institute (NCI) created the Office of Biorepositories and Biospecimen Research (OBBR) to spearhead and coordinate a strategic plan to evaluate and standardize its funded biospecimen resources and the quality of biospecimens used in cancer research.

With the help of the OBBR, the NCI has since developed a set of standards published as the National Cancer Institute Best Practices for Biospecimen Resources.

For more information, please visit:
http://biospecimens.cancer.gov/practices/ or https://cabig.nci.nih.gov



 
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Biospeciman Collection

The path all biospecimens travel from their human source into the research lab for development of new prevention, diagnostic and treatment strategies begins with proper collection. Unless biospecimens are collected and stored in a consistent way, it may not be possible to process them correctly. Molecular properties may change with different types of handling and storage, affecting the quality of interpretation.

     
     
Tissue Collection
Blood Collection
Needle Biopsy Collection

 

Biospecimen Processing

Processing of samples is normally a quality-tested process that is performed the same way on each of the samples in order to minimize variation due to sample handling and preparation for storage.

 

This process usually facilitates long-term storage of a particular sample type. For example, DNA samples are processed into a salt buffer (aqueous solution) at proper pH to stabilize the DNA for storage.

In the image shown here, tissue is being prepared to be embedded in a paraffin block that will preserve it.

As correlative science has moved forward, pathologists have looked in depth at the variables of how tissue is collected and processed and how samples are affected by these variations.

     

 

The following pre-acquisition and post-acquisition variables have been documented:

   

Pre-acquisition Variables:

  • Antibiotics
  • Other drugs
  • Type of anesthesia
  • Duration of anesthesia
  • Arterial clamp time
  • Blood pressure variations
  • Intra-op blood loss
  • Intra-op blood administration
  • Intra-op fluid administration
  • Pre-existing medical conditions
  • Patient gender

Post-aquisition Variables:

  • Time at room tmperature
  • Temperature of room
  • Type of fixative
  • Time in fixative
  • Rate of freezing
  • Size of aliquots
  • Type of collection container
  • Biomolecule extraction method
  • Storage temperature
  • Storage duration
  • Storage in vacuum
   

 

Above is a slide detailing the NCI's procedure for processing biospecimens to ensure standardization. As you can see this does not include standardization prior to freezing or fixing the sample.

 

"Physically tracking the location of a tumor taken from a patient is simple but understanding what goes on inside the tissue between surgery and the freezing/fixation process is not.. Dr David Rim, Pathologist from Yale School of Medicine says, if I look at a piece of tissue that had a one-hour time to fixation and compare it with a 10-minute time to fixation, there are variables in there that are very important to diagnostics." - Quote from CR magazine, a publication of the American Association for Cancer Research.

For more information: http://www.crmagazine.org

We do know that once a sample is taken from a patient and makes its way through the hospital to the pathology lab, it can sit for minutes to hours before it is fixed.

This problem needs to be addressed on the national level as well as at individual institutions as they grapple with how to decrease variations in sample collection and processing. One solution is to freeze the tissue in the operating room before it moves to its final destination.

 

Extensiveness and standardization of annotation

Each sample collected needs to include the same standardized annotation (information, details and measurements), since any biospecimen collection is only as good as the clinical metadata accompanying the biospecimen. The data needs to be complete (extensiveness).

Individual pathologists may use different terms and measurements to say the same thing. A standard is needed. You cannot compare apples to oranges.

 

 

 
   
 
 
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