Burger Maximilian, Burger Sarah J, Denzinger Stefan, Wild Peter J, Wieland Wolf F, Blaszyk Hagen, Obermann Ellen C, Stoehr Robert, Hartmann Arndt
Department of Urology, University of Regensburg, Germany.
Eur Urol. 2006 Oct;50(4):770-5; discussion 776. doi: 10.1016/j.eururo.2006.04.010. Epub 2006 May 2.
The aim of the present study was to evaluate whether elevated microsatellite instability (MSI) at selected tetranucleotide repeats (EMAST) is associated with clinicopathologic and molecular parameters in urinary bladder cancer (BC).
A consecutive series of 117 nonselected urothelial BCs was studied. Microsatellite analysis and detection of loss of heterozygosity (LOH) was performed after microdissection by using 12 markers selected for sensitive detection of EMAST. Furthermore, five markers (BAT25, BAT26, D2S123, APC, and D17S250) of the Bethesda consensus panel for detection of colorectal cancer within the hereditary non-polyposis colon cancer syndrome (HNPCC) were analyzed. Expression of TP53 and mismatch repair (MMR) proteins hMSH2, hMLH1, and hMSH6 was investigated by immunohistochemistry.
EMAST was detected in 10 of 117 patients (8.5%), whereas MSI in the HNPCC panel was found in one of 114 cases (0.9%). LOH in EMAST markers was seen in six of 114 (5.3%) cases. All tumours showed normal expression of hMSH2 and hMLH1. Overexpression of TP53 was observed in nine of 117 evaluated cases (7.7%). No association of EMAST and TP53 expression could be demonstrated. None of the clinicopathologic or molecular parameters were associated with EMAST.
EMAST is another distinct form of MSI in urothelial BC. However, EMAST seems to be a rare event in non-selected urothelial BC and does not seem to be associated with commonly used clinicopathologic and clinical features in patients with BC.
本研究旨在评估选定四核苷酸重复序列处的微卫星不稳定性升高（EMAST）是否与膀胱癌（BC）的临床病理和分子参数相关。
对连续的117例未选择的尿路上皮BC进行研究。在显微切割后，使用12个为敏感检测EMAST而选择的标记物进行微卫星分析和杂合性缺失（LOH）检测。此外，分析了遗传性非息肉病性结肠癌综合征（HNPCC）中用于检测结直肠癌的贝塞斯达共识小组的五个标记物（BAT25、BAT26、D2S123、APC和D17S250）。通过免疫组织化学研究TP53和错配修复（MMR）蛋白hMSH2、hMLH1和hMSH6的表达。
117例患者中有10例（8.5%）检测到EMAST，而114例中有1例（0.9%）在HNPCC小组中检测到微卫星不稳定性（MSI）。114例中有6例（5.3%）在EMAST标记物中出现LOH。所有肿瘤均显示hMSH2和hMLH1表达正常。在117例评估病例中有9例（7.7%）观察到TP53过表达。未发现EMAST与TP53表达之间存在关联。没有任何临床病理或分子参数与EMAST相关。
EMAST是尿路上皮BC中微卫星不稳定性的另一种独特形式。然而，EMAST在未选择的尿路上皮BC中似乎是一种罕见事件，并且似乎与BC患者常用的临床病理和临床特征无关。
