KI-S1 AND PCNA EXPRESSION IN ERYTHROID PRECURSORS AND MEGAKARYOCYTES - A COMPARATIVE-STUDY ON PROLIFERATIVE AND ENDOREDUPLICATIVE ACTIVITY IN REACTIVE AND NEOPLASTIC BONE-MARROW LESIONS

The monoclonal antibody Ki-S1 reacts with a cell proliferation-associa ted nuclear antigen which is expressed in the G1 through G2/M phases o f the cell cycle and is resistant to formalin fixation. We have studie d Ki-S1 and PCNA (PC10) immunostaining of erythroid precursors (prolif erative activity) and megakaryocytes (endoreduplicative activity) in b one marrow trephine biopsies in a variety of reactive and neoplastic l esions using double immunohistochemistry to identify both cell lineage s. A significant increase in Ki-S1 labelling compared with PCNA positi vity was found in all conditions studied. In particular, specimens der ived from secondary polycythaemia (SP), polycythaemia vera (P. vera), and primary osteomyelofibrosis (OMF), and from splenic tissue with mye loid metaplasia (MM), revealed a disproportionally high labelling inde x of erytkropoiesis, which was not present in chronic myelogenous leuk aemia (CML), AIDS, and autoimmune (idiopathic) thrombocytopenia (ITP). Enhancement of Ki-S1 (PCNA) staining in SP and P. vera is in keeping with the relevant increase in erythroid precursor proliferation, but i n OMF and MM there is overexpression of both proliferation markers, po ssibly due to secondary folic acid deficiency, which is known to cause a block in the S-phase of the cell cycle. A significant correlation w as observed between the sizes of megakaryocytes and their nuclei with Ki-S1 (and also PCNA) staining. Ki-S1 (and PCNA) labelling of predomin antly smaller elements of this lineage supports a hypothesis that the phases of the cell cycle have different durations in the various steps of polyploidization, with a prolongation of G1/G2 at higher ploidy le vels. A considerable number of large to giant (hyperpolyploid) megakar yocytes may have reached the end stage of endoreduplicative activity ( Ki-S1-/PCNA-negative GO phase). A comparative evaluation of these two proliferation markers adds significantly to our understanding of cell kinetics in erythro- and megakaryo-poiesis, and sheds some light on th e biological behaviour of these cell lineages in various disorders.