title: A tissue quality index: an intrinsic control for measurement of effects of preanalytical variables on FFPE tissue.
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.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Veronique M
authors.initials: VM
authors.lastname: Neumeister
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Parisi
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: England
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Summar
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Valsamo
authors.initials: V
authors.lastname: Anagnostou
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zarrella
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Vassilakopolou
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Yalai
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Sasha
authors.initials: S
authors.lastname: Saylor
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.affiliation: 1] Department of Pathology, Yale University School of Medicine, New Haven, CT, USA [2] Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Kluger
authors.affiliation: Department of Pathology, University of Rochester School of Medicine, Rochester, NY, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Hicks
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bussolati
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kwei
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D005557:Formaldehyde; D006801:Humans; D016612:Paraffin Embedding; D010336:Pathology / Q000592:standards*; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D013048:Specimen Handling / Q000592:standards*; D013997:Time Factors; D016707:Tissue Fixation
chemical_list: D011960:Receptors, Estrogen; D005557:Formaldehyde