Background: Low frequency epithelial cells occur in bone marrow aspirates of 25-50% of patients with locally confined prostate carcinoma. It is assumed that bone marrow epithelial cells derive from the primary tumor; however, it has not been established unequivocally that they are tumor cells. Immunofluorescence approaches were used to quantify the frequency of epithelial cells in bone marrow aspirates from prostate carcinoma patients and genotypic analyses were used to determine whether they contained numeric aberrations of chromosomes 1, 7, and 8.
Methods: Epithelial cells in bone marrow aspirates collected after radical prostatectomy were visualized using fluorescence microscopy and fluorophore-linked antibodies against cytokeratin 8,18 (CK) and prostate specific antigen (PSA). Antibodies specific for proliferating nuclear cell antigen (PCNA) were used to evaluate the cycling status of discriminated cells. Copies of chromosomes 1, 7, and 8 in the discriminated epithelial cells were quantified using fluorescence in situ hybridization.
Results: CK+ cells were present in bone marrow aspirates from 30 of 66 patients (approximately 45%) at a median frequency of 1.4 CK+ cells/10(5) mononuclear cells. Few CK+ epithelial cells in the bone marrow aspirates coexpressed PSA and none of the CK+ cells expressed PCNA. Approximately 70-75% of the CK+ cells contained 7 and 8 aneusomies. Gains of chromosome 1 occurred in 42% of the CK+ cells.
Conclusions: The majority of CK+ cells in bone marrow aspirates collected after surgery are cytogenetically aberrant, which is consistent with a primary tumor origin. The prevalence and frequency of CK+ cells is independent of tumor stage/grade and androgen treatment.