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Proliferating cell nuclear antigen (PCNA) expression of megakaryocytopoiesis in normal human bone marrow and reactive lesions with special emphasis on HIV-myelopathy

Pathology - Research and Practice
Publication Date
DOI: 10.1016/s0344-0338(11)80495-4
  • Megakaryocytopoiesis
  • Endoreduplication
  • Pcna-Expression
  • Hi V-Mvelopatby
  • Idiopatbic Tbrombocytopenic Purpura
  • Reactive Thrombocytosis
  • Double-Immunostaining
  • Bone Marrow Trephines
  • Biology
  • Economics


Summary A morphometric analysis was performed on bone marrow trephine biopsies using sequential double-immunostaining, to evaluate endoreduplicative activity of megakaryocytopoiesis. A total of 104 marrow specimens were studied with employment of monoclonal antibodies PC1 0 (anti-proliferating cell nuclear antigen - PCNA) and Y21S.1-CD61 (anti-platelet glycoprotein IIIa). In addition to the control group patients included non-specific inflammatory changes, HI V-myelopathy with normal or decreased platelet counts, idiopathic thrombocytopenic purpura (ITP), and finally reactive thrombocytosis (TH). To exclude an undue overexpression of PCNA, in a comparative pilot study we also applied MIB1 (KI-67 antigen) on normal bone marrow specimens. In accordance with the various modalities of cell-cycle marker expression, no significantly different findings were disclosed. PCNA-labelling index was relatively low, ranging from 0.8 to 1.7 % of the total megakaryocytopoiesis (promegakaryoblasts to mature plateletshedding megakaryocytes). A significant relationship between megakaryocyte size and PCNA-expression was determinable. This implies that some of the cases with a prevalence of small megakaryocytes, like ITP, have the tendency to show a higher proportion of positively-stained cells. Moreover, this feature confirms a hypothesis postulating a decrease in the time for DNA-synthesis (S-phase) and a relative prolongation of the Gel G2-phases of the cell-cycle at higher ploidy levels (large-sized megakaryocytes). On the other hand, it may be speculated that some of the hyperpolyplold giant megakaryocytes may have reached their endstage of endoreduplication and enter into Go-phase. In comparison with the control group and the other entities under study, a significant reduction of PCNA-reactivity was recognizable in HIV-myelopathy accompanied by' thrombocytopenia. Our findings are in keeping with cell culture studies assuming that, opposed to ITP and TH, in AIDS different kinetic properties of the megakaryocytic lineage have to be encountered. In this context, it may not entirely be ruled out that viral infection has an inhibitory effect on the stability of mRNA for PCNA and therefore could cause an undue reduction of PCNA-immunostaining.

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