Schwarzenbach Heidi, Chun Felix K-H, Müller Imke, Seidel Christoph, Urban Karoline, Erbersdobler Andreas, Huland Hartwig, Pantel Klaus, Friedrich Martin G
Institute of Tumour Biology, University Medical Centre, Hamburg-Eppendorf, Germany.
BJU Int. 2008 Jul;102(2):253-8. doi: 10.1111/j.1464-410X.2008.07600.x. Epub 2008 Jul 1.
To investigate whether a high frequency of allelic imbalance (AI) is associated with clinicopathological variables of patients with prostate cancer.
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.
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.
Plasma-based MS analysis may have clinical value for the molecular staging of prostate cancer.
研究等位基因不平衡（AI）的高频率是否与前列腺癌患者的临床病理变量相关。
我们在一项基于聚合酶链反应（PCR）的微卫星（MS）研究中，使用一组13个多态性MS标记物，分析了230例前列腺癌患者和43例良性前列腺增生（BPH）患者循环血浆DNA中的杂合性缺失（LOH）和微卫星（MS）不稳定性（MSI）。
原发性肿瘤中AI的总体发生率（34%）显著高于前列腺癌患者血浆样本中的发生率（11%）。虽然在BPH血浆样本中也发现了LOH（2.0%）和MSI（1.5%），但其频率较低。在63%的配对肿瘤样本中可检测到前列腺癌患者血浆样本中鉴定出的AI。在标记物D8S360处，肿瘤和血浆样本之间AI与杂合性保留的最高一致性为83%。在两种类型的标本中，标记物THRB、D7S522和D8S137处的LOH频率较高。染色体臂11q上的标记物D11S898和D11S1313显示出频繁的MSI。与既定风险因素的比较显示，肿瘤组织中联合标记物D6S474/D7S522处以及血浆样本中D7S522处的AI与前列腺体积增加显著相关（P < 0.04）。在原发性肿瘤中，D11S1313处的LOH与总前列腺特异性抗原（tPSA）值升高进一步相关（P = 0.005）。总前列腺特异性抗原（PSA）和游离PSA百分比的组合与血浆样本中THRB处的LOH相关。
基于血浆的MS分析可能对前列腺癌的分子分期具有临床价值。
