Prognostic relevance of disseminated tumour cells in bone marrow of patients with transitional cell carcinoma
Introduction
Several investigations in patients with different tumours (e.g. colorectal cancer, mammary carcinoma, head and neck cancer) have demonstrated the prognostic value of disseminated epithelial tumour cells in bone marrow detected by immunocytochemistry using anti-cytokeratin antibodies.1, 2, 3, 4 To our knowledge, the prognostic relevance of these disseminated cytokeratin-positive (CK+) cells has never been analysed in transitional cell carcinoma (TCC). The majority of tumours are localised in the urinary bladder. The estimated number of incident bladder cancer cases in the European Union was 116,100 in the year 2004.5 Typical features of TCC are multiple localisations and frequent tumour recurrence, often accompanied by tumour progression from a superficial to an invasive tumour stage. In the current prospective study, we analysed the prognostic potential of CK+ cells in bone marrow aspirates from 228 TCC patients to elucidate the changes in tumour cell shedding that might occur dependent on tumour stage and grade and that could give additional information about the patients’ individual outcome.
Section snippets
Patients and bone marrow aspirates
Between June 1990 and July 2001 bone marrow aspirates were taken from 279 unselected patients with transitional cell carcinoma (TCC) after written informed consent was obtained from every patient. The study was approved by the local ethics committee. A total bone marrow volume from 2 to 12 ml was taken from both anterior iliac crests immediately before the start of the surgical procedure (transurethral resection, laser coagulation, nephroureterectomy or cystectomy). Bone marrow analysis and
Results
Cytokeratin-positive cells were detected in 28% (63/228) of the bone marrow samples from TCC patients. The majority of CK+ cases (71%, 45/63) showed only one or two cytokeratin-positive cells in the bone marrow sample (Fig. 2). The range of CK+ cells in the positive cases was 1–100. In January 1994 the antibody CK2 (directed against cytokeratin 18) was replaced by the antibody A45-B/B3, which recognises several cytokeratin subtypes. The expected increase in sensitivity could not be confirmed
Discussion
Patients with TCC show a wide variability in the course of their disease, even when they have comparable tumour stage and grade. In the past years, many studies have examined the detection and prognostic relevance of disseminated tumour cells in patients with various tumours. Most of the monoclonal antibodies used in these studies were directed against cytokeratin to detect epithelial cells in mesenchymal tissue such as bone marrow or peripheral blood. In this prospective study, the frequency
Conflict of interest statement
None declared.
Acknowledgements
The authors thank Barbara Ganzmann, Heinke Mohr, Marion Gerth and Roswitha Fischer for excellent technical assistance, and all the colleagues who performed the bone marrow aspirations. This study was supported by a grant of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; Grant Ho 1596/3).
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- d
These authors contributed equally to the study.