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Asynchronous Growth of Prostate Cancer Is Reflected by Circulating Tumor Cells Delivered from Distinct, Even Small Foci, Harboring Loss of Heterozygosity of the PTEN Gene

¹ Prostate Center, University Clinic; ² Institutes of Pathology and ³ Clinical Chemistry and Laboratory Medicine, and ⁴ Department of Urology, University of Münster, Münster, Germany and ⁵ Institute of Tumor Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

Requests for reprints: Burkhard Brandt, Institute of Tumor Biology Center for Experimental Medicine, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Phone: 49-40-42803-7495; Fax: 49-40-42803-7495; E-mail: bu.brandt{at}uke.uni-hamburg.de.

The clinical value of prostate-specific antigen (PSA)–positive circulating tumor cells (CTCs) is still a matter of debate and it is also still unclear if these CTCs actually represent the primary tumor. Therefore, we isolated PSA-positive CTCs from the peripheral blood of patients suffering from multifocal cancers and did genetic profiling of each cancer focus by a multiplex PCR–based microsatellite analysis (D7S522, D8S522, NEFL, D10S541, D13S153, D16S400, D16S402, D16S422, and D17S855). In 17 of 20 prostate cancer cases, the loss of heterozygosity (LOH) pattern of the CTCs was identical with only one focus of the primary tumor. Moreover, in six cases, the LOH pattern suggested that smaller foci, down to 0.2 cm³, might deliver CTCs. Interestingly, the highest number of LOHs was observed at the marker D10S541 (85%), the PTEN gene, which was observed much less frequently in unifocal prostate cancer (48%). Furthermore, the infrequently occurring LOH in the BRCA1 gene (38%) was found in four of the five cases where a biochemical recurrence was seen within 3 years after prostatectomy. Therefore, the data might support the assumption that CTCs in prostate cancer are derived from distinct foci of a primary tumor. The size of the tumor focus is not related to the delivery of cells. Although the number of cases that were investigated in this study was small, it might be suggested that the LOH at distinct markers such as D10S541 and D17S855 represent the genes PTEN and BRCA1, which might be associated with the occurrence of CTCs in the peripheral blood of patients as well as an early biochemical recurrence. (Cancer Res 2006; 66(18): 8959-65)

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