Cell-free Tumor DNA In Blood Plasma As A Marker For Circulating Tumor Cells In Prostate Cancer

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Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 16 Mar 2009 - 1:00 PDT

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UroToday.com - Dr. Heidi Schwarzenbach and investigators reported on an exciting a new technique to predict for hematogenous tumor spread by detecting cell-free tumor DNA in plasma. Their work appears in the February 1, 2009 issue of Clinical Cancer Research.

The work tested blood plasma and tumor-specific molecular markers relevant for the detection of early micrometastatic spread of prostate cancer (CaP) by combining the detection of circulating tumor cells (CTCs) with the PCR-based microsatellite analysis of cell-free DNA in blood. The PCR assay was a fluorescence microsatellite analysis with a panel of 14 polymorphic markers used for the detection of allelic imbalances (AI). AI includes loss of heterozygosity and microsatellite instability and occurs in both primary tumors and metastases. Often, AI maps to tumor suppressor genes, playing a key role in CaP progression. The immunometric technique used was termed the EPISPOT.

The study cohort included 69 men with localized CaP and 12 with metastatic disease. Genomic DNA from peripheral blood mononuclear cells and plasma samples were amplified by PCR and separated by gel electrophoresis. The genomic DNA served as a reference for calculating the ratio of the intensities to determine AI incidence.

The mean and median values of DNA levels in the blood of metastatic patients were 2-3 times higher than those without metastasis. A control cohort of healthy men was significantly lower with only minor amounts of circulating DNA detectable. AI was detected on cell-free plasma DNA from 45% of non-metastatic patients and 58.5% of metastatic patients. More of the 14 polymorphic markers were affected by LOH in the non-metastatic compared to metastatic patients. No AI at any microsatellite marker used was detected in healthy controls. A positive correlation was found between DNA levels and tumor stages.

CTCs were found in blood of 71% and 92% of the non-metastatic and metastatic patients. More CTCs were found in patients with metastatic CaP. There was a significant correlation between the detection of CTCs and increasing Gleason scores as well as advanced tumor stages in the patients. There was also a significant correlation between the presence of CTCs and the detection of LOH at specific genomic regions.

Schwarzenbach H, Alix-Panabières C, Müller I, Letang N, Vendrell JP, Rebillard X, Pantel K
Clin Cancer Res. 2009 Feb 1;15(3):1032-8
10.1158/1078-0432.CCR-08-1910

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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