Leuraud Pascal, Dezamis Edouard, Aguirre-Cruz Lucinda, Taillibert Sophie, Lejeune Julie, Robin Eric, Mokhtari Karima, Boch Anne-Laure, Cornu Philippe, Delattre Jean-Yves, Sanson Marc
Laboratoire de Biologie des Interactions Neurones-Glie, Institut Nationale de la Santé et de la Recherche Médicale U-495, Service de Neurochirurgie, Fédération de Neurologie Mazarin, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
J Neurosurg. 2004 Feb;100(2):303-9. doi: 10.3171/jns.2004.100.2.0303.
The goal of this study was to examine allelic losses and telomerase activity in meningiomas to determine whether they could be used to predict disease recurrence.
To identify predictive markers of recurrence, a cohort of high-grade (24 World Health Organization [WHO] Grade II and six WHO Grade III) and low-grade (21 WHO Grade I) meningiomas was investigated for losses of heterozygosity (LOHs) on chromosomes 1p, 9p, 10q, 14q, and 22q, a deletion of CDKN2A, and telomerase activity. Results of molecular analyses were compared with radiological and histological findings and progression-free survival (PFS). Losses of heterozygosity on chromosomes 22q, 1p, and 10q, as well as telomerase activity were related to the WHO histological grades of the lesions (p < 0.01, p < 10(-5), p < 10(-4), and p = 0.002, respectively). In the absence of an LOH on 22q, the other alterations were found infrequently. Overall, the number of molecular alterations was closely related to the histological grades of the lesions (p < 10(-6)). An LOH on 22q occurred much more frequently in convexity or falx (33 [87%] of 38 lesions) than in skull base or spinal meningiomas (four [31%] of 13 lesions) (p < 0.001). The histological grade; Simpson grade; an LOH on chromosome 1p, 9p, or 10q; and telomerase activity were correlated with a shorter PFS time (p < 10(-4), p = 0.02, p = 0.000365, p = 0.022, p = 0.00027, and p = 0.000512, respectively).
On the basis of these data the authors suggest that LOH analysis and a telomerase activity assay could be useful to determine molecular predictors of outcome in patients with meningiomas.
本研究的目的是检测脑膜瘤中的等位基因缺失和端粒酶活性，以确定它们是否可用于预测疾病复发。
为了确定复发的预测标志物，对一组高级别（24例世界卫生组织[WHO]二级和6例WHO三级）和低级别（21例WHO一级）脑膜瘤进行了1p、9p、10q、14q和22q染色体上的杂合性缺失（LOH）、CDKN2A缺失以及端粒酶活性检测。将分子分析结果与放射学和组织学结果以及无进展生存期（PFS）进行比较。22q、1p和10q染色体上的杂合性缺失以及端粒酶活性与病变的WHO组织学分级相关（分别为p < 0.01、p < 10⁻⁵、p < 10⁻⁴和p = 0.002）。在22q不存在杂合性缺失的情况下，很少发现其他改变。总体而言，分子改变的数量与病变的组织学分级密切相关（p < 10⁻⁶）。22q上的杂合性缺失在凸面或大脑镰脑膜瘤中出现的频率（38例病变中的33例[87%]）远高于颅底或脊髓脑膜瘤（13例病变中的4例[31%]）（p < 0.001）。组织学分级、辛普森分级、1p、9p或10q染色体上的杂合性缺失以及端粒酶活性与较短的无进展生存期相关（分别为p < 10⁻⁴、p = 0.02、p = 0.000365、p = 0.022、p = 0.00027和p = 0.000512）。
基于这些数据，作者认为杂合性缺失分析和端粒酶活性检测可能有助于确定脑膜瘤患者预后的分子预测指标。
