Platelet-derived growth factor receptor β (PDGFRβ) immunohistochemistry highlights activated bone marrow stroma and is potentially predictive for fibrosis progression in prefibrotic myeloproliferative neoplasia

G. Méhes, Alexandar Tzankov, Konnie Hebeda, Ioannis Anagnostopoulos, L. Krenács, Judit Bedekovics

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aims: 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. Methods and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)617-624
Number of pages8
JournalHistopathology
Volume67
Issue number5
DOIs
Publication statusPublished - Nov 1 2015

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Platelet-Derived Growth Factor Receptors
Primary Myelofibrosis
Fibrosis
Bone Marrow
Immunohistochemistry
Neoplasms
Reticulin
Stromal Cells
Sensitivity and Specificity
Fibroblasts
Staining and Labeling
Biopsy
Myeloproliferative Disorders
Disease Progression

Keywords

  • Bone marrow
  • Immunohistochemistry
  • Platelet-derived growth factor receptor
  • Primary myelofibrosis

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

Platelet-derived growth factor receptor β (PDGFRβ) immunohistochemistry highlights activated bone marrow stroma and is potentially predictive for fibrosis progression in prefibrotic myeloproliferative neoplasia. / Méhes, G.; Tzankov, Alexandar; Hebeda, Konnie; Anagnostopoulos, Ioannis; Krenács, L.; Bedekovics, Judit.

In: Histopathology, Vol. 67, No. 5, 01.11.2015, p. 617-624.

Research output: Contribution to journalArticle

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abstract = "Aims: 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. Methods and 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. Conclusion: 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.",
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AU - Anagnostopoulos, Ioannis

AU - Krenács, L.

AU - Bedekovics, Judit

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N2 - Aims: 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. Methods and 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. Conclusion: 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.

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