Sustaining proliferative signaling
Proliferating cell nuclear antigen expression by erythroid precursors in normal bone marrow, in reactive lesions and in polycythaemia rubra vera.
Using a sequential double-immunostaining technique, a morphometric analysis was performed on routinely processed bone marrow trephines from 20 patients with secondary (reactive) polycythaemia and 28 patients with polycythaemia rubra vera to determine the proliferation capacity of erythropoiesis. Monoclonal antibodies PC10--anti-proliferating cell nuclear antigen (PCNA)--and Ret40f--anti-glycophorin C--were employed. For comparison with the PCNA-labelling index, in a pilot study, Ki-67 was additionally used on frozen-section material. In comparison with normal bone marrow (15 patients) morphometric and statistical evaluation revealed a numerical increase in erythroid precursors (pro-, erythro- and normoblasts) in secondary polycythaemia and to a pronounced degree in polycythaemia rubra vera. In comparison with secondary polycythaemia and the control group, in polycythaemia rubra vera there was a significant enhancement of proliferation according to PCNA-staining reactivity in all haematopoietic cell elements and particularly in the erythroid series. Evaluation of PCNA v. Ki-67 immunostaining disclosed only a slight difference, which could be mainly attributed to various modalities of antigen expression during the cell cycle. Our findings are in keeping with in vitro studies on cultured erythroid progenitor cells and, in problematic cases, may present a valuable aid in differentiation between reactive lesions and polycythaemia rubra vera.