Catto James W F, Azzouzi Abdel-Rahmene, Amira Najla, Rehman Ishtiaq, Feeley Kenneth M, Cross Simon S, Fromont Gaelle, Sibony Mathilde, Hamdy Freddie C, Cussenot Oliver, Meuth Mark
The Institute for Cancer Studies, University of Sheffield, UK.
Oncogene. 2003 Nov 27;22(54):8699-706. doi: 10.1038/sj.onc.1206964.
To date, two forms of microsatellite instability (MSI) have been described in human cancer. MSI typical of hereditary nonpolyposis colon cancer (HNPCC), is due to deficient DNA mismatch repair (MMR) and is defined with mono- and dinucleotide repeat microsatellites. A second variety of instability is best seen at selective tetranucleotide repeats (EMAST; elevated microsatellite alterations at select tetranucleotides). While MSI occurs infrequently in bladder cancers, EMAST is common. Sporadic tumours with the largest proportion showing MSI are those found most frequently in HNPCC kindreds. While bladder cancer is not frequently seen in HNPCC, upper urinary tract tumours (UTTs) are. Having previously found a low frequency of MSI in bladder cancer, we sought to determine the relative levels of MSI and EMAST in transitional cell carcinoma (TCC) of the upper and lower urinary tracts. Microsatellite analysis was performed at 10 mono- and dinucleotide and eight tetranucleotide loci, in 89 bladder and 71 UTT TCC. Contrasting patterns of instability were seen in urinary tumours. In bladder cancer, MSI was rare and EMAST was common. The presence of EMAST was not related to tumour grade, stage, subsequent outcome or immunohistochemical expression of the MMR proteins. In UTT, while MSI occurred frequently, EMAST was seen less frequently than in bladder cancer. When TCC of the upper and lower urinary tracts are compared, MSI-H is more frequent in UTT and EMAST more frequent in bladder cancer. Our findings show that, as for colorectal cancer, the pattern of MSI varies with location in the urinary tract. In addition, we have confirmed that MSI and EMAST are discrete forms of MSI, and that the presence of EMAST does not affect tumour phenotype.
迄今为止，人类癌症中已描述了两种形式的微卫星不稳定性（MSI）。遗传性非息肉病性结直肠癌（HNPCC）典型的MSI是由于DNA错配修复（MMR）缺陷所致，通过单核苷酸和二核苷酸重复微卫星来定义。第二种不稳定性在选择性四核苷酸重复序列（EMAST；选择性四核苷酸处微卫星改变增加）中最为明显。虽然MSI在膀胱癌中很少见，但EMAST很常见。散发性肿瘤中显示MSI比例最高的是那些在HNPCC家族中最常发现的肿瘤。虽然HNPCC中不常见膀胱癌，但上尿路肿瘤（UTT）却很常见。此前我们发现膀胱癌中MSI的频率较低，因此我们试图确定上尿路和下尿路移行细胞癌（TCC）中MSI和EMAST的相对水平。在89例膀胱癌和71例UTT TCC中，对10个单核苷酸和二核苷酸以及8个四核苷酸位点进行了微卫星分析。在泌尿系统肿瘤中观察到了不同的不稳定性模式。在膀胱癌中，MSI罕见而EMAST常见。EMAST的存在与肿瘤分级、分期、后续转归或MMR蛋白的免疫组化表达无关。在UTT中，虽然MSI频繁发生，但EMAST的出现频率低于膀胱癌。当比较上尿路和下尿路的TCC时，MSI-H在UTT中更常见，而EMAST在膀胱癌中更常见。我们的研究结果表明，与结直肠癌一样，MSI模式随尿路位置而变化。此外，我们已经证实MSI和EMAST是MSI的不同形式，并且EMAST的存在不影响肿瘤表型。
