Eckert Anika, Kloor Matthias, Giersch Antje, Ahmadi Rezvan, Herold-Mende Christel, Hampl Jürgen A, Heppner Frank L, Zoubaa Saida, Holinski-Feder Elke, Pietsch Torsten, Wiestler Otmar D, von Knebel Doeberitz Magnus, Roth Wilfried, Gebert Johannes
Department of Applied Tumor Biology, University Hospital Heidelberg, Heidelberg, Germany.
Brain Pathol. 2007 Apr;17(2):146-50. doi: 10.1111/j.1750-3639.2007.00049.x.
About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (approximately 25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms.
约15%的散发性胃肠道和子宫内膜肿瘤因DNA错配修复（MMR）功能缺失而表现出微卫星不稳定（MSI）表型。中枢神经系统肿瘤中MSI的发生率仍存在争议。先前的研究报道，患有高级别胶质瘤的年轻患者中MSI的发生率特别高（约25%）。基于这些数据以及在不同肿瘤实体中MMR缺陷定义了一组具有独特发病机制和特定临床病理特征的肿瘤亚组，这些特征可能对预后和治疗产生影响，我们使用三种高度敏感的诊断标志物，通过MSI分析对71名年轻患者和553名成年患者的624例胶质瘤进行了MMR缺陷筛查。通过免疫组织化学检查MMR蛋白表达的改变。一名成年患者的恶性胶质瘤显示出MSI，并伴有核MSH2和MSH6蛋白表达缺失（0.16%；1/619）。在71例年轻患者的胶质瘤中未观察到MSI或MMR蛋白表达缺失的证据（0%；0/71），其中包括41例高级别星形细胞瘤。总体而言，我们观察到高级别儿童胶质瘤中MSI的发生率远低于最初报道的水平，并表明MMR缺陷在胶质肿瘤的发病机制中不发挥主要作用。
