Prognostic value of single micrometastatic cells detected in bone marrow of prostate cancer patients

D. Weckermann MD^a, B. Polzer, MD^b, M. Hamm,MD^a, F. Wawroschek, MD^a, R. Harzmann, MD^a, C Klein, MD^b

Aims: Single cytokeratin (CK) positive tumor cells in bone marrow (BM) indicate the occult dissemination of cancer cells. In contrast to other epithelial tumors our previous investigations have shown that CK18-positive bone marrow cells in prostate cancer (CaP) neither correlate with established prognostic factors nor with the biochemical and clinical course after radical prostatectomy (RP). For a better understanding of minimal residual disease after complete resection of the primary tumor and its transition to systemic progression we now studied the fate of CK18+ cells isolated from patients with different clinical courses and analyzed their genomic organization by single cell comparative genomic hybridization (SCOMP). Methods: BM aspirations were taken from 214 patients with locoregional and N+-adenocarcinoma of the prostate prior to radical prostatectomy, repeated after 6 months for the first time and then in yearly intervals. We first evaluated the significance of CK18+ cells in BM on the biochemical course and then asked whether CK18+ cells persist in patients with and without biochemical relapse and after hormonal therapy. In parallel, from exemplary patients we isolated single CK18+ cells by micromanipulation, amplified their genomic DNA and performed SCOMP. Results: Patients with biochemical progression showed an increase of CK18+ cells after RP. Interestingly, CK18+ cells persisted for years after RP even in patients with complete remission, whereas CK18+ tumor cells regularly disappeared under hormonal therapy. Comparative genomic hybridization with amplified genomic DNA of these isolated cells revealed multiple chromosomal aberrations. Conclusions: Tumor cells survive in BM for several years after RP, even in men who seem to be cured. It remains to be seen whether particular genomic aberrations or patterns of aberrations are associated with tumor dormancy and systemic progression of CaP.

KEY WORDS: cytokeratin staining, single cell genomic hybridization, tumor dormancy.

For more information, contact Dr.Weckermann@t-online.de

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Chromatin Structures.

This presentation received an honorable mention in our poster contest and was recognized with the Symposium Presidents' Award for Scientific Excellence.

http://www.cancerprev.org/Journal/Issues/26/101/995/4192