Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome

J Clin Pathol. 2015 May;68(5):381-7. doi: 10.1136/jclinpath-2014-202728. Epub 2015 Jan 30.

Abstract

Aims: To study the immunoexpression of proteins related to the mitotic checkpoint (cell division cycle 20 (CDC20), mitotic arrest deficient 2 (MAD2)) and the mitotic spindle (Aurora-B) in patients with myelodysplastic syndrome (MDS).

Methods: Protein expression was analysed in bone marrow tissue samples from 40 patients with MDS using immunohistochemistry. Prognostic markers (transfusion dependency, depth of cytopenias, chromosomal abnormalities and survival) were also studied.

Results: Higher MAD2 expression was observed among patients with platelets <50×10(9)/L than among patients with platelets ≥50×10(9)/L (42.6±22.8% vs 22.7±19.1%, respectively). Higher CDC20 expression was identified among patients with three dysplasias compared with patients who presented with one or two dysplasias (33.9±24.1% vs 10.5±5.7% vs 12.8±7.8%, respectively), among patients who exhibited a complex versus non-complex karyotype (50.0±30.2% vs 18.4±14%, respectively) and among patients with platelets <50×10(9)/L vs platelets ≥50×10(9)/L (38.2±26.2% vs 16.1±12.4%, respectively). Higher Aurora-B expression was found in patients with an abnormal versus normal karyotype (21.2±13.2% vs 7.5±5.0%, respectively). High expression of MAD2 and CDC20 (≥50%) was associated with severe thrombocytopenia. We also found statistically significant differences in the overall survival rate when comparing different degrees of CDC20, MAD2 and Aurora-B protein expression.

Conclusions: To the best of our knowledge, this is the first report to demonstrate that these proteins are associated with chromosomal abnormalities and poor prognosis in patients with MDS.

Keywords: HEMATOPATHOLOGY; IMMUNOHISTOCHEMISTRY; MYELODYSPLASIA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aurora Kinase B / analysis*
  • Bone Marrow / chemistry*
  • Bone Marrow / pathology
  • Cdc20 Proteins / analysis*
  • Chromosomal Instability*
  • Chromosome Banding
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Karyotype
  • M Phase Cell Cycle Checkpoints*
  • Mad2 Proteins / analysis*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / blood
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / metabolism*
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / pathology
  • Platelet Count
  • Prognosis
  • Retrospective Studies
  • Spindle Apparatus / chemistry*
  • Thrombocytopenia / blood
  • Thrombocytopenia / genetics
  • Thrombocytopenia / metabolism
  • Young Adult

Substances

  • Cdc20 Proteins
  • MAD2L1 protein, human
  • Mad2 Proteins
  • CDC20 protein, human
  • AURKB protein, human
  • Aurora Kinase B