Microsatellite analysis of allelic imbalance in tumour and blood from patients with prostate cancer.
OBJECTIVE
To investigate whether a high frequency of allelic imbalance (AI) is associated with clinicopathological variables of patients with prostate cancer.


METHODS
We analysed loss of heterozygosity (LOH) and microsatellite (MS) instability (MSI) on circulating plasma DNA in a polymerase chain reaction (PCR)-based MS study of 230 patients with prostate cancer and 43 with benign prostatic hyperplasia (BPH) using a panel of 13 polymorphic MS markers.


RESULTS
The overall incidence of AI was significantly higher in primary tumours (34%) than in blood plasma samples from patients with prostate cancer (11%). Although LOH (2.0%) and MSI (1.5%) were also found in BPH plasma samples, their frequencies were low. AI identified in plasma samples from patients with prostate cancer could be retrieved in 63% of the paired tumour samples. The highest concordance of AI and retention of heterozygosity between tumour and plasma samples was 83% at the marker D8S360. There were high frequencies of LOH at the markers THRB, D7S522 and D8S137 in both types of specimens. The markers D11S898 and D11S1313 on the chromosome arm 11q showed frequent MSI. The comparison with established risk factors showed significant associations of an increase in prostate volume with AI at the combined markers D6S474/D7S522 in tumour tissues and at D7S522 in plasma samples (P < 0.04). In the primary tumours there was a further correlation of LOH at D11S1313 with increasing tPSA value (P = 0.005). The combination of total prostate-specific antigen (PSA) and % free PSA was associated with LOH at THRB in plasma samples.


CONCLUSIONS
Plasma-based MS analysis may have clinical value for the molecular staging of prostate cancer.
Schwarzenbach
Heidi
H
Institute of Tumour Biology, University Medical Centre, Hamburg-Eppendorf, Germany. hschwarz@uke.uni-hamburg.de
Chun
Felix K-H
FK
Müller
Imke
I
Seidel
Christoph
C
Urban
Karoline
K
Erbersdobler
Andreas
A
Huland
Hartwig
H
Pantel
Klaus
K
Friedrich
Martin G
MG
D022981:Allelic Imbalance / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood*; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm; D005819:Genetic Markers; D017430:Prostate-Specific Antigen