Disseminated cytokeratin positive tumor cells in the bone marrow of patients with prostate cancer:: Detection and prognostic value

Purpose: Previous investigations have shown that cytokeratin 18 positive bone marrow cells in localized and lymphatically spread prostate cancer correlates with neither established prognostic factors nor with the biochemical and clinical course after radical prostatectomy. Since the well-known down-regulation of cytokeratin 18 in tumor cells may lead to false-negative results, we asked whether staining with a pan-cytokeratin antibody recognizing a common epitope of cytokeratins 8, 18 and 19 would result in different data. Materials and Methods: Preoperative bone marrow aspirates of 82 patients with localized (NO) and lymphatically spread (N1) prostate cancer were examined using the monoclonal antibody cytokeratin 2 and the pan-cytokeratin antibody A 45-B/B3, called A 45. Results: In contrast to findings with the cytokeratin 18 antibody, those with the pancytokeratin antibody correlated with the biochemical course. At a median followup of 1,477 days (4 years) patients with pan-cytokeratin positive cells in the preoperative bone marrow aspirate had biochemical progression significantly earlier than those with pan-cytokeratin negative results (mean time to prostate specific antigen relapse 886 versus 1,409 days, p less than or equal to0.004). Compared with other parameters, such as prostate specific antigen, pathological stage and Gleason score, preoperative pan-cytokeratin findings proved to be an independent prognostic factor. Conclusions: Cytokeratin positive cells in the bone marrow also have prognostic relevance in prostate cancer. The comprehensive analysis of these cells, studies of the individual course of these findings and sufficiently long followup allow us to discuss whether and under what conditions metastasis may develop from 1 or several cytokeratin positive cells.