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Lab Invest. 2014 Apr;94(4):467-74. doi: 10.1038/labinvest.2014.7. Epub 2014 Feb 17.

A tissue quality index: an intrinsic control for measurement of effects of preanalytical variables on FFPE tissue.

Author information

1
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
2
Department of Medical Sciences, University of Turin, Turin, Italy.
3
1] Department of Pathology, Yale University School of Medicine, New Haven, CT, USA [2] Department of Medical Sciences, University of Turin, Turin, Italy.
4
Department of Pathology, University of Rochester School of Medicine, Rochester, NY, USA.
5
Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.

Abstract

While efforts are made to improve tissue quality and control preanalytical variables, pathologists are often confronted with the challenge of molecular analysis of patient samples of unknown quality. Here we describe a first attempt to construct a tissue quality index (TQI) or an intrinsic control that would allow a global assessment of protein status based on quantitative measurement of a small number of selected, informative epitopes. Quantitative immunofluorescence (QIF) of a number of proteins was performed on a series of 93 breast cancer cases where levels of expression were assessed as a function of delayed time to formalin fixation. A TQI was constructed based on the combination of proteins that most accurately reflect increased and decreased levels of expression in proportion to delay time. The TQI, defined by combinations of measurements of cytokeratin, ERK1/2 and pHSP-27 and their relationship to cold ischemic time were validated on a second build of the training series and on two independent breast tissue cohorts with recorded time to formalin fixation. We show an association of negative TQI values (an indicator for loss of tissue quality) with increasing cold ischemic time on both validation cohorts and an association with loss of ER expression levels on all three breast cohorts. Using expression levels of three epitopes, we can begin to assess the likelihood of delayed time to fixation or decreased tissue quality. This TQI represents a proof of concept for the use of epitope expression to provide a mechanism for monitoring tissue quality.

PMID:
24535259
PMCID:
PMC4030875
DOI:
10.1038/labinvest.2014.7
[Indexed for MEDLINE]
Free PMC Article
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