title: Platelet-derived growth factor receptor β (PDGFRβ) immunohistochemistry highlights activated bone marrow stroma and is potentially predictive for fibrosis progression in prefibrotic myeloproliferative neoplasia.
abstract: OBJECTIVE
  Myelofibrosis is the result of aberrant stromal activity which is determined routinely by reticulin staining in bone marrow biopsies. As matrix fibres are the product of activated fibroblasts, we analysed fibre accumulation compared to stromal cell activity during myelofibrosis progression using the fibroblast activation marker platelet-derived growth factor receptor β (PDGFRβ) by immunohistochemistry.
  
  
  RESULTS
  Initial and follow-up bone marrow biopsies from 84 patients with myeloproliferative neoplasia, including 55 cases with primary myelofibrosis, were evaluated from five haematopathology centres. The stromal mass was measured by conventional reticulin staining [myelofibrosis (MF) grade, 0-3] and PDGFRβ-positive cells using a novel PDGFRβ scoring system (0-3). Results were correlated for prediction of progression. The MF grade and the PDGFRβ score showed excellent correlation (Spearman's r = 0.83, P < 0.0001). Elevated PDGFRβ scores (higher than MF-grade) predicted myelofibrosis progression in total with 43% sensitivity and 57% specificity, and short-term (within 1 year) progression with 82% sensitivity and 53% specificity. Progression of prefibrotic disease to manifest myelofibrosis could be forecast with 90% sensitivity and 75% specificity.
  
  
  CONCLUSIONS
  PDGFRβ highlights stromal cell activation in marrow fibrosis, which is closely related to matrix accumulation, indicating a direct clinical impact especially in prefibrotic myeloproliferative disorders.
authors.affiliation: Department of Pathology, University of Debrecen, Debrecen, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Méhes
authors.affiliation: Institute of Pathology, University Hospital, Basel, Switzerland.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.affiliation: Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Konnie
authors.initials: K
authors.lastname: Hebeda
authors.affiliation: Institute of Pathology, Charité-University Medicine Berlin, Campus Charité Mitte, Berlin, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.affiliation: Laboratory of Tumor Pathology and Molecular Diagnostics, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Krenács
authors.affiliation: Department of Pathology, University of Debrecen, Debrecen, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Bedekovics
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D009196:Myeloproliferative Disorders / Q000473:pathology*; D055728:Primary Myelofibrosis / Q000473:pathology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: bone marrow; immunohistochemistry; platelet-derived growth factor receptor; primary myelofibrosis