Sood A K, Holmes R, Hendrix M J, Buller R E
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Holden Cancer Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242-1109, USA.
Cancer Res. 2001 Jun 1;61(11):4371-4.
Recently, the National Cancer Institute (NCI) established criteria for determination of microsatellite instability (MSI) in colorectal tumors. Although the best panel of markers for ovarian tumors is not known, we evaluated epithelial ovarian cancers for MSI based on the NCI recommendations. One hundred and nine ovarian tumors were analyzed for MSI by gel analysis of paired germ-line and tumor DNA. PCR amplification was performed using the panel of five microsatellite markers recommended by the NCI (BAT25, BAT26, D5S346, D2S123, and D17S250) and nine additional markers picked based on their genomic location (NME1, D10S197, D11S904, D13S175, DXS981, DXS6800, DXS6807, AR, and D3S1611). Tumors were characterized on the basis of: high-frequency MSI (MSI-H) if two or more of the five NCI markers showed instability or there was instability at 30% or more of all markers tested; or low-frequency MSI (MSI-L) if only one of the five NCI markers showed instability or <30% of all of the markers. All of the other tumors were considered microsatellite stable. On the basis of the NCI markers, 12 (11%) tumors demonstrated MSI-H, and 8 (7%) additional tumors had MSI-L. When all of the 14 markers were considered together, 13 (12%) tumors demonstrated MSI-H (based on 30% or more unstable loci), and 26 (24%) tumors had MSI-L. A single tumor identified to have MSI-H based upon all of the markers tested would have been classified as MSI-L based upon the NCI markers alone. Inclusion of an additional dinucleotide marker (NME1) to the NCI panel allowed detection of all of the tumors with MSI-H using only six markers. MSI-H occurs in approximately 12% of invasive ovarian tumors. For optimal detection of microsatellite instability in ovarian cancer, an additional marker (NME1) may be required, along with the five recommended by the NCI.
最近，美国国立癌症研究所（NCI）制定了判定结直肠肿瘤微卫星不稳定性（MSI）的标准。尽管目前尚不清楚用于卵巢肿瘤的最佳标记物组合，但我们根据NCI的建议对上皮性卵巢癌进行了MSI评估。通过对配对的种系DNA和肿瘤DNA进行凝胶分析，对109例卵巢肿瘤进行了MSI分析。使用NCI推荐的五个微卫星标记物组合（BAT25、BAT26、D5S346、D2S123和D17S250）以及另外九个根据其基因组位置挑选的标记物（NME1、D10S197、D11S904、D13S175、DXS981、DXS6800、DXS6807、AR和D3S1611）进行PCR扩增。肿瘤的特征基于以下标准判定：如果五个NCI标记物中的两个或更多显示不稳定，或者在所有测试标记物中有30%或更多显示不稳定，则为高频MSI（MSI-H）；如果五个NCI标记物中只有一个显示不稳定，或者所有标记物中<30%显示不稳定，则为低频MSI（MSI-L）。所有其他肿瘤被认为是微卫星稳定的。基于NCI标记物，12例（11%）肿瘤表现为MSI-H，另外8例（7%）肿瘤为MSI-L。当将所有14个标记物一起考虑时，13例（12%）肿瘤表现为MSI-H（基于30%或更多不稳定位点），26例（24%）肿瘤为MSI-L。仅根据NCI标记物，一个经所有测试标记物鉴定为MSI-H的肿瘤会被归类为MSI-L。在NCI标记物组合中加入一个额外的二核苷酸标记物（NME1），仅使用六个标记物就能检测出所有MSI-H肿瘤。MSI-H在约12%的浸润性卵巢肿瘤中出现。为了最佳地检测卵巢癌中的微卫星不稳定性，可能需要一个额外的标记物（NME1）以及NCI推荐的五个标记物。
