title: Image analysis of platelet derived growth factor receptor-beta (PDGFRβ) expression to determine the grade and dynamics of myelofibrosis in bone marrow biopsy samples.
abstract: BACKGROUND
  Myelofibrosis (MF) is characterized by accumulation of stromal cells and extracellular matrix. Progression of fibrosis is an important clinical issue and monitoring is required for new therapeutic approaches. Currently, the quantification is based on semiquantitative evaluation of reticulin silver stained slides. We recently reported that platelet derived growth factor receptor beta (PDGFRβ) expression in fibroblasts is a useful marker of stromal activation. PDGFRβ expression based scores represent significant differences in different MF grade which provides optimal source of quantification. In this study, slide-based measurements were performed to support correlations of PDGFRβ expression with MF grade.
  
  
  METHODS
  Scanned image tiles from 79 bone marrow samples (BM) with different MF grades were evaluated for PDGFRβ-related IHC parameters. Following the determination of immunopositive (brown component) and total area (region of interest) of the BM, PDGFRβ related image parameters were defined and evaluated in comparison with the classical reticulin based grading.
  
  
  RESULTS
  Eight PDGFRβ expression related image parameters showed excellent correlation with the MF grade (correlation coefficient ranging between 0.79 and 0.83) and with PDGFRβ score (0.76-0.87). Despite the significant sample heterogeneity, the parameters showed significant differences between fibrotic and nonfibrotic cases and between mild and advanced fibrosis. Distribution of values within a particular specimen emphasizes the heterogeneity of bone marrow involvement which may cause difficulties in semiquantitative methods.
  
  
  CONCLUSIONS
  Our results clearly demonstrated the correlation between MF and PDGFRβ expression considering all relevant areas in BM samples. This method provides good basis for follow-up comparison of the fibrotic samples.
authors.affiliation: Department of Pathology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Bedekovics
authors.forename: Szilvia
authors.initials: S
authors.lastname: Szeghalmy
authors.forename: Lívia
authors.initials: L
authors.lastname: Beke
authors.forename: Attila
authors.initials: A
authors.lastname: Fazekas
authors.forename: Gábor
authors.initials: G
authors.lastname: Méhes
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D005109:Extracellular Matrix; D005355:Fibrosis / Q000473:pathology*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000473:pathology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis*; D012155:Reticulin / Q000032:analysis; D016622:Silver Staining / Q000379:methods; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D012155:Reticulin; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: PDGFRβ expression in myelofibrosis; bone marrow biopsy; digital image analysis; myeloproliferative neoplasia