title: Tissue microarray technique is applicable to bone marrow biopsies of myeloproliferative neoplasms.
abstract: Tissue microarray (TMA) technique is an established high-throughput method to analyze multiple tissue specimens in parallel. However, in order to obtain reliable results from immunohistochemical analyses of TMA blocks, cell composition of TMA spots must correspond to whole tissue sections (WTS) particularly in tissues with a heterogeneous cell composition as it is the case in myeloproliferative neoplasms (MPN). The aim of this study was to validate TMA of bone marrow biopsies from MPN patients. TMAs of MPN bone marrow biopsies (ET: n = 26, PV: n = 26, and PMF: n = 29) were compiled in triplicates and MPN-specific histological parameters were assessed. Results of TMA spots were compared with WTS' results using the intra-class correlation coefficient (ICC). Immunohistochemical NFE2 and calreticulin stainings of the TMA with quantitative evaluation were performed. TMA construction was technically successful with a loss of 10 % of all spots. ICC calculation revealed high to moderate correlations of TMA with WTS, especially the parameters that are typically affected in MPN tissue, e.g. cellularity of hematopoiesis (ICC 0.62-0.89), number of megakaryocytes (ICC 0.50-0.71), micro-vessel density (ICC 0.56-0.91), or grade of myelofibrosis (ICC 0.56-0.89). Results of NFE2 and calreticulin immunohistochemistry of MPN TMAs are consistent with previously published data. Overall, our results show moderate to good correlation between histological data of WTS and TMA spots illustrating that the TMA technique is applicable to bone marrow biopsies of MPN patients. However, TMA construction in triplicates is necessary to reach sufficient correlation. MPN TMAs can be applied for serial immunohistochemical surveys of archived tissues to assess the mutation status or to further sub-classify MPN cases.
authors.affiliation: Institue for Surgical Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 115a, 79106, Freiburg im Breisgau, Germany.|General and Visceral Surgery, Schwarzwaldbaar-Klinikum Villingen, Villingen-Schwenningen, Germany.
authors.forename: Kathrin A
authors.initials: KA
authors.lastname: Limberger
authors.affiliation: Institute for Medical Biometry and Medical Informatics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Lioudmila
authors.initials: L
authors.lastname: Bogatyreva
authors.affiliation: Institue for Surgical Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 115a, 79106, Freiburg im Breisgau, Germany.
authors.forename: Rumyana
authors.initials: R
authors.lastname: Todorova
authors.affiliation: Institue for Surgical Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 115a, 79106, Freiburg im Breisgau, Germany.|Comprehensive Cancer Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Herde
authors.affiliation: Institute for Medical Biometry and Medical Informatics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Hauschke
authors.affiliation: Department of Medicine I, Hematology, Oncology, and Stem- Cell Transplantation, Division of Molecular Hematology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Heike L
authors.initials: HL
authors.lastname: Pahl
authors.affiliation: Institue for Surgical Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 115a, 79106, Freiburg im Breisgau, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.affiliation: Institue for Surgical Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Strasse 115a, 79106, Freiburg im Breisgau, Germany. konrad.aumann@uniklinik-freiburg.de.
authors.forename: Konrad
authors.identifier: http://orcid.org/0000-0001-8178-1571
authors.initials: K
authors.lastname: Aumann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000473:pathology*; D046888:Tissue Array Analysis; D055815:Young Adult
keywords: Immunohistochemistry; Myeloproliferative neoplasms; Tissue microarray; Validation