title: Detection of circulating tumor cells from renal carcinoma patients: experiences of a two-center study.
abstract: Approximately 30-40% of primary and localized renal cell carcinoma (RCC) will eventually become metastatic disease. Therefore, the detection and molecular characterization of circulating tumor cells (CTC) in RCC may have important prognostic and therapeutic implications. Venous blood samples were obtained from a total of 214 RCC patients before and after nephrectomy or during adjuvant immune chemotherapy in two urological centers. After density gradient centrifugation, the CD45-negative cell population was isolated from peripheral blood samples (BS) by a semi-automated immunomagnetic depletion procedure using the MACS technology. Enriched cell populations potentially containing CTC were stained for cytokeratin and evaluated by a trained pathologist. CTC were found in 105 out of 363 BS (29%) originating from 80 out of 214 patients (37%). The median tumor cell number was five (range 1-51) per BS, i.e. approximately one CTC was detectable per 2-3 ml peripheral blood after tumor cell enrichment. For a subpopulation, follow-up data indicate that 62% of the patients with CTC detection in the blood developed progressive disease with single or multiple distant metastases or died because of RCC within two years. Here we show that the standardized immunomagnetic depletion protocol is a powerful tool for detecting and isolating intact RCC-derived CTC. The occurrence and the quantity of CTC in RCC patients is an early disease event. Furthermore, the occurrence of CTC is correlated with an advanced tumor stage and seems to be associated with a more aggressive tumor phenotype.
authors.affiliation: Clinic of Urology, University Halle-Wittenberg, Ernst-Grube-Str. 4, D-06120 Halle/Saale, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Blümke
authors.forename: Udo
authors.initials: U
authors.lastname: Bilkenroth
authors.forename: Uta
authors.initials: U
authors.lastname: Schmidt
authors.forename: Andres
authors.initials: A
authors.lastname: Melchior
authors.forename: Susanne
authors.initials: S
authors.lastname: Füssel
authors.forename: Frank
authors.initials: F
authors.lastname: Bartel
authors.forename: Hans
authors.initials: H
authors.lastname: Heynemann
authors.forename: Paolo
authors.initials: P
authors.lastname: Fornara
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Wirth
authors.forename: Axel
authors.initials: A
authors.lastname: Meye
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D002469:Cell Separation; D002499:Centrifugation, Density Gradient; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008280:Magnetics; D008297:Male; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D007633:Keratins; D017493:Leukocyte Common Antigens