Berger Andreas P, Parson Walther, Stenzl Arnulf, Steiner Hannes, Bartsch Georg, Klocker Helmut
Department of Urology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Eur Urol. 2002 May;41(5):532-9. doi: 10.1016/s0302-2838(02)00073-8.
Bladder cancer is the result of clonal expansion of cancer cells in which multiple genetic alterations have occurred. Loss of heterozygosity (LOH) studies have demonstrated that alterations in microsatellite regions are common in bladder cancer. This observation offers the possibility of early tumor detection by examining the DNA of urinary sediment.
We investigated alterations of 17 microsatellite loci in urinary bladder carcinomas of different stages and grades. Per locus, 19-30 specimens were evaluated. DNA was isolated from tumor specimens, urinary sediment and peripheral blood lymphocytes. DNA fragments of 17 microsatellite loci were amplified by PCR and analyzed for genomic alterations.
Microsatellite alterations were detected in tumor tissue and urine sediment from 27 out of 31 patients (87%). Urine sediment analysis alone proved positive in 24 out of 31 patients (77%). The type of lesions most frequently detected was LOH (74% of all alterations), followed by length alteration (24%) and additional alleles (2%). On average, the alteration frequency was 22% per locus. The loci at chromosomes 9 and 18 proved most informative. No alterations were found in grade I tumors. The study revealed a correlation between microsatellite alterations and the respective grades and stages of the tumors. Average alteration frequencies per locus were: 27.4% in grade III versus 19.3% in grade II tumors, 26.5% in invasive versus 12.3% in superficial tumors.
Our results demonstrate that microsatellite alterations are common in bladder cancer and that analysis of genomic instabilities in urine samples should be further evaluated as a method for bladder cancer screening in a high-risk group. Especially, when a set of microsatellites is used that shows a high probability of detecting alterations and allows easy handling, this could be an alternative or a completion to currently available methods.
膀胱癌是癌细胞克隆性扩增的结果，在此过程中发生了多种基因改变。杂合性缺失（LOH）研究表明，微卫星区域的改变在膀胱癌中很常见。这一观察结果为通过检测尿沉渣DNA进行早期肿瘤检测提供了可能性。
我们研究了不同分期和分级的膀胱癌中17个微卫星位点的改变。每个位点评估19 - 30个标本。从肿瘤标本、尿沉渣和外周血淋巴细胞中分离DNA。通过聚合酶链反应（PCR）扩增17个微卫星位点的DNA片段，并分析基因组改变。
31例患者中的27例（87%）肿瘤组织和尿沉渣中检测到微卫星改变。仅尿沉渣分析在31例患者中的24例（77%）呈阳性。最常检测到的病变类型是LOH（占所有改变的74%），其次是长度改变（24%）和额外等位基因（2%）。平均每个位点的改变频率为22%。9号和18号染色体上的位点信息最为丰富。I级肿瘤未发现改变。该研究揭示了微卫星改变与肿瘤的相应分级和分期之间的相关性。每个位点的平均改变频率为：III级肿瘤为27.4%，II级肿瘤为19.3%；浸润性肿瘤为26.5%，浅表性肿瘤为12.3%。
我们的结果表明微卫星改变在膀胱癌中很常见，尿样中基因组不稳定性的分析应作为高危人群膀胱癌筛查的一种方法进一步评估。特别是，当使用一组显示出高概率检测到改变且易于操作的微卫星时，这可能是现有方法的一种替代或补充。
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