Detection of occult micrometastases in the bone marrow of patients with prostate carcinoma

A panel of three monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (T16, C26, and AE-1) was used in a sensitive immunohistochemical assay to detect tumor cells in bone marrow aspirates from 20 patients with prostate cancer. Bone marrow aspirates from 2/9 (22%) patients with localized prostate cancer (stage B, 0/5; Stage C, 2/4), and 4/11 (36%) patients with metastatic prostate cancer (Stage D1, 0/7 patients; Stage D2, 4/4 patients) had antigen-positive cells in their bone marrow. The patients with localized disease had conventional examinations for metastases, including radioisotope bone scans and examination of bone marrow cytology, which were negative. The serum prostatic specific antigen (PSA) level appeared to correlate with the presence of micrometastases. Those patients with localized disease and antigen-positive cells in the bone marrow had an average serum PSA level of 26.6 ng/ml, while the average serum PSA level in patients without antigen-positive cells was 12.3 ng/ml. In addition, the number of antigen-positive cells detected appeared to correlate with the stage of disease; patients with Stage C prostate cancer had an average of 10 antigen-positive cells per one million bone marrow elements, while patients with Stage D2 disease had an average of 25 antigen-positive cells per one million bone marrow elements. We have demonstrated that immunohistochemical staining of bone marrow aspirates can detect occult bone marrow metastases in patients with apparently localized prostate cancer. Further follow-up of these and a larger number of patients will be require to determine the potential clinical significance of this finding.