THE PROGNOSTIC IMPACT OF CYTOKERATIN-POSITIVE CELLS IN BONE MARROW OF PATIENTS WITH LOCALIZED PROSTATE CANCER

Abstract
Background: The prognosis of patients with localized prostate cancer depends on clinical stage, histological grade, and pretreatment serum PSA level. We evaluated whether the additional parameter of the presence of circulating prostate cancer cells in the bone marrow (BM) or peripheral blood (PB) is associated with failure-free survival in patients with prostate cancer suitable for curative local treatment. Material and methods: We evaluated pre-treatment BM/PB samples of 66 patients with T1-3pN0M0 prostate cancer for the presence of isolated tumor cells. The patients underwent definitive radiotherapy. The presence of cytokeratin-positive cells (CK+) cells was based on APAAP-technique using the immunocytochemical staining of AE1/AE3 cytokeratin antibodies against epithelial epitopes. Positive control staining was carried out with MOPC-21 monoclonal antibody in all BM/PB samples. Median folllow-up duration in the present study was 65 months (range: 46-78 months). Results: A total of 14 patients (21%) had CK+ cells in the BM/PB pre-treatment sample. In 12 of 60 patients (20%) 1-400 CK+ cells were observed in BM (median 2 cells). The presence of CK+ cells in the posttreatment BM sample was significantly correlated with progression-free survival (p = 0.02), whereas this was not the case for the presence of such cells in the pretreatment BM sample. Conclusion: In summary, the presence of CK+ cells (20%) in bone marrow > 18 months after definitive radiotherapy in patients with localized prostate cancer is associated with decreased progression-free survival. These patients may be candidates for clinical trials assessing adjuvant systemic treatment. However, our results need confirmation in a larger cohort of patients before it can be routinely used in the clinic.

Key words
Prostate cancer, micrometastases, bone marrow, immunocytochemistry

Bibliografía del artículo

1. Fowler FJ, Jr., McNaughton Collins M et al. Comparison of recommendations by urologists and radiation oncologists for treatment of clinically localized prostate cancer. Jama 2000;283(24):3217-22.
2. Scardino PT, Hanks GE. A comparison of prostate cancer treatments: are therapeutic implications justified Cancer J Sci Am 1997;3(2):70-2.
3. Hanks GE, Hanlon AL, Epstein B et al. Dose response in prostate cancer with 8-12 years' follow-up. Int J Radiat Oncol Biol Phys 2002;54(2):427-35.
4. Schellhammer PF, El-Mahdi AM, Kuban DA et al. Prostate-specific antigen after radiation therapy. Prognosis by pretreatment level and post-treatment nadir. Urol Clin North Am 1997;24(2):407-14.
5. Lange PH, Vessella RL. Mechanisms, hypotheses and questions regarding prostate cancer micrometastases to bone. Cancer Metastasis Rev 1998;17(4):331-6.
6. Pantel K, Otte M. Occult micrometastasis: enrichment, identification and characterization of single disseminated tumour cells. Semin Cancer Biol 2001;11(5):327-37.
7. Naume B, Borgen E, Nesland JM et al. Increased sensitivity for detection of micrometastases in bone-marrow/peripheral-blood stem-cell products from breast-cancer patients by negative immunomagnetic separation. Int J Cancer 1998;78(5):556-60.
8. Borgen E, Beiske K, Trachsel S et al. Immunocytochemical detection of isolated epithelial cells in bone marrow: non-specific staining and contribution by plasma cells directly reactive to alkaline phosphatase. J Pathol 1998;185(4):427-34.
9. Borgen E, Naume B, Nesland JM et al. Use of automated microscopy for the detection of disseminated tumor cells in bone marrow samples. Cytometry 2001;46(4):215-21.
10. Funke I, Schraut W. Bone marrow metastases in breast cancer. N Engl J Med 2000;343(8):577; discussion 578.
11. Wood DP Jr, Banerjee M. Presence of circulating prostate cells in the bone marrow of patients undergoing radical prostatectomy is predictive of disease-free survival. J Clin Oncol 1997;15(12):3451-7.
12. Weckermann D, Muller P, Wawroschek F et al. Disseminated cytokeratin positive tumor cells in the bone marrow of patients with prostate cancer: detection and prognostic value. J Urol 2001;166(2):699-703.
13. Mehes G, Witt A, Kubista E et al. Circulating breast cancer cells are frequently apoptotic. Am J Pathol 2001;159(1):17-20.
14. ASTRO. Consensus statement: guidelines for PSA following radiation therapy. American Society for Therapeutic Radiology and Oncology Consensus Panel. Int J Radiat Oncol Biol Phys 1997;37(5):1035-41.
15. Bolla M, De Reijke TM, Zurlo A et al. Adjuvant hormone therapy in locally advanced and localized prostate cancer: three EORTC trials. Front Radiat Ther Oncol 2002;36:81-6.
16. Roach M 3rd, Lu J, Pilepich MV et al. Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials. Int J Radiat Oncol Biol Phys 2000;47(3):617-27.
17. Pollack A, Joon DL, Wu CS et al. Quiescence in R3327-G rat prostate tumors after androgen ablation. Cancer Res 1997;57(12):2493-500.
18. Pantel K, Enzmann T, Kollermann J et al. Immunocytochemical monitoring of micrometastatic disease: reduction of prostate cancer cells in bone marrow by androgen deprivation. Int J Cancer 1997;71(4):521-5.
19. Murphy GP, Tjoa BA, Simmons SJ et al. Phase II prostate cancer vaccine trial: report of a study involving 37 patients with disease recurrence following primary treatment. Prostate 1999;39(1):54-9.

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