Reduction of Preanalytical Variability in Specimen Procurement for Molecular Profiling View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2012

AUTHORS

Virginia Espina , Claudius Mueller

ABSTRACT

Despite the tremendous perceived value, and the predicted high abundance, of disease-associated tissue biomarkers, the number of biomarkers that have been validated for routine clinical use is very low. The major roadblock has been the sample-to-sample variability and perishability of biomolecules in tissue. A chief source of variability is biomolecule perturbation caused by sample handling, the time delays following procurement, and the method of preservation. Living tissue that has been separated from its blood supply during surgical procurement goes through defined stages of reactive changes preceding death, beginning with oxidative, hypoxic, and metabolic stress. These reactive fluctuations in the tissue biomolecules can occur within 20 min postexcision, and can significantly distort the levels of critical diagnostic and prognostic biomolecules. Depending on the delay time ex vivo, and manner of handling, protein biomarkers such as signal pathway phosphoproteins will be elevated or suppressed in a manner that does not represent the biomarker levels at the time of excision. Based on analysis of phosphoproteins, one of the most labile tissue protein biomarkers, we set forth tissue procurement guidelines for clinical research. We further propose the future use of a multipurpose fixative solution designed to stabilize, preserve and maintain proteins, nucleic acids, and tissue architecture. More... »

PAGES

49-57

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/978-1-60327-216-2_4

DOI

http://dx.doi.org/10.1007/978-1-60327-216-2_4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1011306964

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22081338


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45 schema:description Despite the tremendous perceived value, and the predicted high abundance, of disease-associated tissue biomarkers, the number of biomarkers that have been validated for routine clinical use is very low. The major roadblock has been the sample-to-sample variability and perishability of biomolecules in tissue. A chief source of variability is biomolecule perturbation caused by sample handling, the time delays following procurement, and the method of preservation. Living tissue that has been separated from its blood supply during surgical procurement goes through defined stages of reactive changes preceding death, beginning with oxidative, hypoxic, and metabolic stress. These reactive fluctuations in the tissue biomolecules can occur within 20 min postexcision, and can significantly distort the levels of critical diagnostic and prognostic biomolecules. Depending on the delay time ex vivo, and manner of handling, protein biomarkers such as signal pathway phosphoproteins will be elevated or suppressed in a manner that does not represent the biomarker levels at the time of excision. Based on analysis of phosphoproteins, one of the most labile tissue protein biomarkers, we set forth tissue procurement guidelines for clinical research. We further propose the future use of a multipurpose fixative solution designed to stabilize, preserve and maintain proteins, nucleic acids, and tissue architecture.
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