title: Cellular proliferation and prevalence of micrometastatic cells in the bone marrow of patients with clinically localized prostate cancer.
abstract: The presence of prostate cancer cells in the bone marrow (BM) of patients with clinically localized disease is associated with an increased chance of disease recurrence; however, not all patients develop recurrence. We therefore sought to determine the phenotype of individual micrometastatic cells as a potential method to better predict disease outcome. Immunostaining was performed on BM cells from 46 patients whose BM RNA fraction had been identified to contain prostate-specific antigen mRNA. The prevalence of micrometastatic cells among BM mononuclear cells was determined using an anticytokeratin antibody. Mib-1 antibody was used to determine the percentage of micrometastatic cells that were proliferating. Micrometastatic cells were found in 96% of patient samples, with a 30-fold variation in prevalence ranging from 0.1-3.26/10(5) BM cells. Prior androgen ablation was associated with a reduced prevalence of micrometastatic cells (P = 0.010). In 68% of patients, some micrometastatic cells were judged to be proliferating at proportions ranging from 1 of 11 (9%) to 4 of 4 (100%). Higher Gleason score of the primary tumor was associated with a higher proliferative proportion of micrometastatic cells (P = 0.038). We conclude that, in patients with clinically localized disease, there is wide variability in the prevalence of micrometastatic cells and the proportion which are proliferating. Long-term follow-up will determine whether the development of clinically obvious metastatic disease is related to higher prevalence of micrometastatic cells in the marrow or the proportion that are proliferating.
authors.affiliation: Department of Urology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. mcher@med.wayne.edu
authors.forename: M L
authors.initials: ML
authors.lastname: Cher
authors.forename: J G
authors.initials: JG
authors.lastname: de Oliveira
authors.forename: A A
authors.initials: AA
authors.lastname: Beaman
authors.forename: J A
authors.initials: JA
authors.lastname: Nemeth
authors.forename: M
authors.initials: M
authors.lastname: Hussain
authors.forename: D P
authors.initials: DP
authors.lastname: Wood
mesh_terms: D001853:Bone Marrow / Q000473:pathology*; D019046:Bone Marrow Neoplasms / Q000473:pathology* / Q000556:secondary*; D002453:Cell Cycle; D002455:Cell Division; D006801:Humans; D008297:Male; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000473:pathology*; D014410:Tumor Stem Cell Assay