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Cellular Proliferation and Prevalence of Micrometastatic Cells in the Bone Marrow of Patients with Clinically Localized Prostate Cancer¹

Departments of Urology [M. L. C., J. G. d. O., A. A. B., J. A. N., D. P. W.] and Pathology [M. L. C.] and the Division of Medical Oncology [M. H.], Wayne State University School of Medicine, and The Genitourinary Oncology Program of The Barbara Ann Karmanos Cancer Institute [M. L. C., M. H., D. P. W.], Detroit, Michigan 48201

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 0.1–3.26/10⁵ 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.