LOW-FREQUENCY EPITHELIAL-CELLS IN BONE-MARROW ASPIRATES FROM PROSTATECARCINOMA PATIENTS ARE CYTOGENETICALLY ABERRANT

BACKGROUND. Low frequency epithelial cells occur in bone marrow aspira tes 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 ar e 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 wheth er they contained numeric aberrations of chromosomes 1, 7, and 8. METH ODS. Epithelial cells in bone marrow aspirates collected after radical prostatectomy were visualized using fluorescence microscopy and fluor ophore-linked antibodies against cytokeratin 8, 18 (CK) and prostate s pecific antigen (PSA). Antibodies specific for proliferating nuclear c ell antigen (PCNA) were used to evaluate the cycling status of discrim inated cells. Copies of chromosomes 1, 7, and 8 in the discriminated e pithelial cells were quantified using fluorescence in situ hybridizati on. RESULTS. CK+ cells were present in bone marrow aspirates from 30 o f 66 patients (approximately 45%) at a median frequency of 1.4 CK+ cel ls/10(5) mononuclear cells. Few CK+ epithelial cells in the bone marro w aspirates coexpressed PSA and none of the CK+ cells expressed PCNA. Approximately 70-75% of the CK+ cells contained 7 and 8 aneusomies. Ga ins of chromosome 1 occurred in 42% of the CK+ cells. CONCLUSIONS. The majority of CK+ cells in bone marrow aspirates collected after surger y are cytogenetically aberrant, which is consistent with a primary tum or origin. The prevalence and frequency of CK+ cells is independent of tumor stage/grade and androgen treatment. [See editorial on pages 394 -8, this issue.] Cancer 1998;83:538-46. (C) 1998 American Cancer Socie ty.