Wong Yick Fu, Cheung Tak Hong, Lo Keith Wing Kit, Yim So Fan, Chan Loucia Kit Yin, Buhard Olivier, Duval Alex, Chung Tony Kwok Hung, Hamelin Richard
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China and Inserm, U762, Paris, F-75010 France;, Univ Paris 6, Paris, F-75005 France.
Carcinogenesis. 2006 May;27(5):951-5. doi: 10.1093/carcin/bgi333. Epub 2006 Feb 20.
The aim of this study was to find the optimal set of microsatellite markers for diagnosis of the microsatellite instability (MSI) phenotype in endometrial cancers. We compared the sensitivity, specificity and ease of use of a reference panel of five markers originally recommended by the National Cancer Institute (NCI) for colorectal cancer and a panel of five quasi-monomorphic mononucleotide repeat markers (pentaplex PCR system). We used these panels for establishing the MSI status of a series of 80 sporadic endometrial adenocarcinomas by comparing the allelic profiles of the markers between tumor and matching germline DNA. Both panels detected the same subset of 21 out of 80 (26%) endometrial MSI carcinomas. However, in the MSI cases, the mean instability of the five mononucleotide repeats was 96.1% as compared with a mean instability of 69.8% for the three dinucleotide repeats of the NCI panel, indicating a superiority of mononucleotide repeats over dinucleotide repeats in detecting MSI. The fact that the two panels of markers detect the same set of MSI tumors is due to the presence of two mononucleotide repeats within the NCI panel. As demonstrated previously in gastric and colon MSI cases, the pentaplex PCR reaction using mononucleotide repeats is thus an easier and more sensitive method than the NCI panel, for the screening of MSI status in endometrial tumors.
本研究的目的是找到用于诊断子宫内膜癌微卫星不稳定性（MSI）表型的最佳微卫星标记组合。我们比较了美国国立癌症研究所（NCI）最初推荐用于结直肠癌的五个标记物的参考组合以及一个由五个准单态单核苷酸重复标记物组成的组合（五重PCR系统）的敏感性、特异性和易用性。我们通过比较肿瘤和匹配的种系DNA之间标记物的等位基因谱，使用这些组合来确定一系列80例散发性子宫内膜腺癌的MSI状态。两个组合在80例（26%）子宫内膜MSI癌中检测到相同的21例子集。然而，在MSI病例中，五个单核苷酸重复序列的平均不稳定性为96.1%，而NCI组合的三个二核苷酸重复序列的平均不稳定性为69.8%，这表明在检测MSI方面单核苷酸重复序列优于二核苷酸重复序列。两个标记物组合检测到相同的MSI肿瘤集，这一事实是由于NCI组合中存在两个单核苷酸重复序列。因此，如先前在胃癌和结肠癌MSI病例中所证明的，使用单核苷酸重复序列的五重PCR反应是一种比NCI组合更简便、更灵敏的方法，用于筛查子宫内膜肿瘤的MSI状态。
