Coven İlker, Ozer Ozge, Ozen Ozlem, Şahin Feride İffet, Altinors Nur
Departments of Neurosurgery.
J Neurosurg. 2014 Dec;121(6):1478-82. doi: 10.3171/2014.8.JNS13515. Epub 2014 Sep 26.
Meningiomas are benign extraaxial tumors with a slow progression. Some of them, in spite of being benign in nature, may show an aggressive progression pattern. To investigate the behavioral characteristics of meningiomas, researchers have studied matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), interstitial collagens, proteins, vascular endothelial growth factors (VEGF), and tumor necrosis factors.
In this study, the authors investigated MMP2 and TIMP2 gene polymorphisms in formalin-fixed paraffin-embedded tissue samples obtained from meningioma patients who had previously undergone surgery at the authors' institution. In addition, brain invasion, Ki-67 index, and MMP-2 and TIMP-2 expressions were investigated using immunohistochemical methods. MMP2 (735C>T, 1575G>A, 1306C>T) and TIMP2 (418G>C, 303C>T) gene polymorphisms were investigated from paraffin-embedded tissue sections using the polymerase chain reaction-restriction fragment length polymorphism method.
There were statistically significant differences between genotype (p = 0.001) and allele frequencies (p = 0.001 and OR 7.4 [95% CI 1.5-36.2]) in patient and control groups for MMP2 1306C>T polymorphism. The authors did not find a statistically significant difference for other polymorphisms. GA genotype was found to be more frequent when brain invasion was suspected for MMP2 1575G>A polymorphism (p = 0.006). There was not a statistically significant difference for other MMP2 or TIMP2 gene polymorphisms.
The authors' results support the importance of MMPs and their tissue inhibitors in meningioma pathogenesis. In future studies, these gene polymorphisms, especially MMP2 1306C>T and 1575G>A, should be investigated for meningioma or brain invasion susceptibility in larger study groups.
脑膜瘤是一种进展缓慢的良性轴外肿瘤。其中一些肿瘤尽管本质上是良性的,但可能呈现侵袭性进展模式。为了研究脑膜瘤的行为特征,研究人员对基质金属蛋白酶(MMPs)、其组织抑制剂(TIMPs)、间质胶原、蛋白质、血管内皮生长因子(VEGF)和肿瘤坏死因子进行了研究。
在本研究中,作者调查了从曾在作者所在机构接受手术的脑膜瘤患者获得的福尔马林固定石蜡包埋组织样本中的MMP2和TIMP2基因多态性。此外,采用免疫组织化学方法研究了脑侵袭、Ki-67指数以及MMP-2和TIMP-2的表达。使用聚合酶链反应-限制性片段长度多态性方法从石蜡包埋组织切片中研究MMP2(735C>T、1575G>A、1306C>T)和TIMP2(418G>C、303C>T)基因多态性。
MMP2 1306C>T多态性在患者组和对照组的基因型(p = 0.001)和等位基因频率(p = 0.001,优势比7.4 [95%可信区间1.5 - 36.2])上存在统计学显著差异。作者未发现其他多态性存在统计学显著差异。对于MMP2 1575G>A多态性,当怀疑有脑侵袭时,GA基因型更为常见(p = 0.006)。其他MMP2或TIMP2基因多态性不存在统计学显著差异。
作者的结果支持MMPs及其组织抑制剂在脑膜瘤发病机制中的重要性。在未来的研究中,应在更大的研究群体中研究这些基因多态性,尤其是MMP2 1306C>T和1575G>A,以探讨其与脑膜瘤或脑侵袭易感性的关系。