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Detection of tumor‐specific DNA in blood and bone marrow plasma from patients with prostate cancer
Author(s) -
Schwarzenbach Heidi,
Chun Felix K.H.,
Lange Imke,
Carpenter Sebastian,
Gottberg Miriam,
Erbersdobler Andreas,
Friedrich Martin G.,
Huland Hartwig,
Pantel Klaus
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22470
Subject(s) - bone marrow , circulating tumor cell , pathology , prostate cancer , loss of heterozygosity , medicine , cytokeratin , primary tumor , cancer , blood plasma , metastasis , biology , immunohistochemistry , gene , allele , biochemistry
Tumor tissues, blood plasma and bone marrow (BM) aspirates of 57 prostate cancer patients (PCa) without clinical signs of overt metastases were assessed for LOH (loss of heterozygosity) by a PCR‐based fluorescence microsatellite analysis, using a panel of 15 markers. Additionally, micrometastatic tumor cells in BM were monitored by an immunocytological cytokeratin assay. In total, 25 (44%), 32 (56%) and 41 (72%) of the patients had at least 1 LOH in their blood, BM and tumor samples, respectively. Among the informative cases, the frequency of LOH was highest in blood plasma for the markers D8S360 (18%) and D10S1765 (15%), and in BM plasma for THRB (24%) and D8S137 (22%). Comparison of blood plasma and BM with tumors showed discrepant results in 35% and 45% of patients, respectively. Whereas all LOHs at THRB in BM plasma were also detected in the autologous tumor tissues, LOHs at D6S474 and D11S898 in BM were not retrieved in the tumors. The comparison with established risk factors showed a correlation of borderline significance for LOH at D9S1748 in the BM aspirates ( p = 0.055) and a significant correlation in the tumor samples ( p = 0.004) with increasing pathologic Gleason scores. Interestingly, 22% of the PCa patients harbored tumor cells in their BM and tended ( p = 0.065) to have more frequent LOH (16%) in BM plasma compared to patients without tumor cells (9%). These data demonstrate, for the first time, the presence of free tumor‐specific DNA in blood and BM of PCa patients and suggest a possible relationship to BM micrometastasis. © 2006 Wiley‐Liss, Inc.