Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Eur J Neurol. 2012 Feb;19(2):298-306. doi: 10.1111/j.1468-1331.2011.03509.x. Epub 2011 Sep 6.
Seizures are a common symptom of patients with primary brain tumors, particularly low-grade gliomas (LGGs). Poor seizure control after surgery has a great adverse impact on quality of life in these patients. The present study aimed to identify clinical and molecular genetic factors that influence postoperative seizure control.
A series of 183 LGGs were analyzed by denaturing high-performance liquid chromatography (DHPLC) for 1p and 19q status and by immunohistochemical staining for expression of several molecular markers (P53, Ki-67, MMP-9 and MGMT), with particular emphasis on correlations with postoperative seizure control. Univariate and multivariate logistic regression analyses were used for statistic analysis.
Of the 183 patients, 134 (73.2%) patients presented with seizures. Most of oligodendrogliomas and oligoastrocytomas had LOH 1p and LOH 19q, which were rarely seen in combination in astrocytomas (P<0.001). Oligodendroglial tumors were more likely to locate in frontal lobe (P=0.011) and present calcification on MRI (P=0.024). Temporal location (P=0.014), and high expression of mutated P53 (P=0.011) were associated with astrocytomas. Patients achieved much better seizure control after gross-total resection (P<0.001) than after subtotal resection. Patients without LOH 19q were more likely to have poor seizure control (P=0.004) than those with this alteration. Ki-67 was an independent molecular marker predicting poor seizure control (P=0.016) if over expressed.
Gross total resection of the tumor, LOH 19q and low Ki-67 expression were associated with favorable seizure control after surgery for the patients with LGGs. The possible involvement of other factors should be investigated further.
癫痫是原发性脑肿瘤患者的常见症状,尤其是低级别胶质瘤(LGG)患者。术后癫痫控制不佳对这些患者的生活质量有很大的负面影响。本研究旨在确定影响术后癫痫控制的临床和分子遗传因素。
通过变性高效液相色谱法(DHPLC)分析了 183 例 LGG 的 1p 和 19q 状态,并通过免疫组织化学染色检测了几种分子标志物(P53、Ki-67、MMP-9 和 MGMT)的表达,特别强调了与术后癫痫控制的相关性。采用单因素和多因素逻辑回归分析进行统计学分析。
在 183 例患者中,134 例(73.2%)患者出现癫痫。大多数少突胶质细胞瘤和少突星形细胞瘤存在 1p 和 19q 的杂合性缺失,但在星形细胞瘤中很少同时出现(P<0.001)。少突胶质细胞瘤更倾向于位于额叶(P=0.011),并且在 MRI 上有钙化(P=0.024)。肿瘤位于颞叶(P=0.014)和 P53 突变高表达(P=0.011)与星形细胞瘤相关。与次全切除相比,肿瘤大体全切除的患者术后癫痫控制更好(P<0.001)。无 19q 杂合性缺失的患者术后癫痫控制不佳的可能性高于有此改变的患者(P=0.004)。Ki-67 过度表达是预测术后癫痫控制不佳的独立分子标志物(P=0.016)。
肿瘤大体全切除、19q 杂合性缺失和 Ki-67 低表达与 LGG 患者术后癫痫控制良好相关。可能涉及其他因素,应进一步调查。