E26转录因子与基质金属蛋白酶9在脑膜瘤中的表达及相关性研究

目的研究E26转录因子(Ets-1)和基质金属蛋白酶9(MMP-9)在脑膜瘤中的表达及相关性。方法采用免疫组织化学法检测56例脑膜瘤石膜标本(良性组39例、恶性倾向组17例)中Ets-1和MMP-9的表达,采用逆转录聚合酶链反应(RT-PCR)方法检测30例新鲜脑膜瘤(良性组22例,恶性倾向组8例)中Ets-1和MMP-9的mRNA水平。另取9例行脑外伤减压术的正常脑组织作为对照组结果正常脑组织Ets-1和MMP-9不表达或低表达,脑膜瘤中Ets-1阳性表达率48.2%(27/56),MMP-9阳性表达率62.5%(35/56);脑膜瘤恶性倾向组Ets-1和MMP-9的阳性表达率高于脑膜瘤良性组(P<0.05);Ets-1和MMP-9在脑膜瘤中的表达呈正相关(rs=0.284,P<0.05)。脑膜瘤中Ets-1和MMP-9的mRNA含量高于正常脑组织(P<0.05),脑膜瘤恶性倾向组Ets-1和MMP-9的mRNA含量高于脑膜瘤良性组(P<0.05),Ets-1和MMP-9在脑膜瘤的mRNA水平呈正相关(r=0.479、P<0.02)。结论Ets-1和MMP-9的表达与脑膜瘤恶性度有关,两者在脑膜瘤发生、发展过程中有协同作用,可作为脑膜瘤预后的潜在指标。     

脑膜瘤中miR-200b和ZEB1的表达水平变化及其与预后的关系

目的 探讨脑膜瘤组织中miR-200b、ZEB1表达水平变化与脑膜瘤患者预后的关系。方法 选择2013年5月-2014年12月在本院行神经外科手术治疗的脑膜瘤患者42例,采用qRT-PCR法检测各研究对象脑膜瘤组织与瘤旁组织中miR-200b表达水平,采用免疫组织化学染色法检测ZEB1水平,分析miR-200b、ZEB1表达水平与脑膜瘤临床病理特征的相关性,并对出院后的脑膜瘤患者进行随访,分析miR-200b、ZEB1表达水平变化与脑膜瘤患者预后的关系。结果 脑膜瘤组织miR-200b表达水平显著低于瘤旁组织(P<0.05); 脑膜瘤组织ZEB1阳性表达率高于瘤旁组织(P<0.05); miR-200b、ZEB1表达水平与肿瘤分期有关(P<0.05); miR-200b高表达组的5年无瘤生存率显著高于miR-200b低表达组,ZEB1阳性表达组的5年无瘤生存率显著低于ZEB1阴性表达组(P<0.05); miR-200b低表达、ZEB1阳性表达可能是脑膜瘤患者不良预后的独立危险因素。结论 在脑膜瘤组织中miR-200b低表达、ZEB1阳性表达,且与患者无瘤生存期有关,可作为判断脑膜瘤患者预后的潜在标志物。     

人脑膜瘤VEGF的表达和微血管检测及临床意义

目的探讨人脑膜瘤血管内皮细胞生长因子(VEGF)的表达和微血管数量(MVQ)与肿瘤良恶性程度的关系。方法用免疫组织化学染色方法检测手术切除石蜡包埋的36例脑膜瘤(良性27例,恶性9例)组织中的VEGF蛋白表达情况与MVQ数量,显微镜下观察其阳性细胞数和阳性血管数。结果①良、恶性脑膜瘤组织中均有VEGF和MVQ表达,且主要表达于肿瘤细胞的胞浆和血管内皮细胞胞膜中;良、恶性脑膜瘤VEGF表达的阳性率分别为77.8%、100%,有显著性差异(P<0.05);VEGF表达阳性的MVQ平均值(47.6±8.5)高于阴性组(24.3±7.9),差异有统计学意义(P <0.01)。②VEGF的表达与MVQ值相关(r =0.75,P <0.01)。结论VEGF在脑膜瘤血管生成中起重要作用,能促进脑膜瘤血管的形成;VEGF和MVQ与脑膜瘤良、恶性程度明显相关,可作为脑膜瘤病理诊断的补充指标之一,并为脑膜瘤的基因治疗提供依据。     

P53和P57kip2在脑膜瘤中的表达及临床意义

目的探讨P53和P57kip2在脑膜瘤中的表达及临床意义。方法应用免疫组化SP法检测41例脑膜瘤组织和21例正常脑膜组织中P53和P57kip2蛋白的表达。结果在脑膜瘤中两者的阳性表达率:P53 48.78%,P57kip241.46%;P53在恶性脑膜瘤中的阳性率(75.00%)显著高于良性脑膜瘤及正常组织中的阳性率(P<0.05);P57kip2在恶性脑膜瘤中的阳性率(25.00%)显著低于于良性脑膜瘤及正常组织中的阳性率(P<0.05);P53与P57kip2在脑膜瘤中的表达呈负相关。结论 P53和P57kip2分别是脑膜瘤进展及预后判断的独立指标,多个指标联合检查用来估计患者预后指导意义更佳。     

胶质瘤患者肿瘤组织和血浆中MMP-9的表达及意义

目的探讨胶质瘤患者肿瘤组织和血浆中基质金属蛋白酶-9(MMP-9)的表达、两者之间的关系及意义。方法收集40例胶质瘤患者病理标本、患者术前血浆及临床资料,分成高度恶性组和低度恶性组。10例因重度颅脑损伤而行内减压手术切除的脑组织和患者术前血浆,作为对照组。运用免疫组织化学染色法对胶质瘤组织标本中MMP-9表达进行半定量分析。运用酶联免疫吸附测定法检测血浆中总MMP-9浓度。结果 MMP-9在正常脑组织中无表达,高度恶性组瘤组织中MMP-9的表达显著高于低度恶性组(P=0.027)和对照组(P=0.000)。各级别胶质瘤组MMP-9血浆浓度均显著高于对照组(P0.001)。瘤组织MMP-9强阳性表达组血浆MMP-9浓度显著高于阴性组(P=0.022)和弱阳性组(P=0.048),血浆MMP-9浓度与相应肿瘤组织MMP-9的表达水平呈正相关(rs=0.530,P=0.000)。结论瘤组织MMP-9表达与胶质瘤恶性程度呈正相关,其高表达可能与胶质瘤的侵袭转移有关;胶质瘤患者血浆MMP-9浓度一定程度上反映出瘤组织中MMP-9表达水平。     

脑膜瘤MMP-9表达及其对血管形成、脑浸润和瘤周水肿的影响

目的 探讨脑膜瘤中基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达和临床病理学意义。方法 应用免疫组织化学SP法检测52例脑膜瘤组织中MMP-9表达情况,并结合临床病理参数进行综合分析。结果 MMP-9的表达与脑膜瘤病理分级、微血管密度(MVD)、侵袭行为、瘤周水肿显著相关(P<0.05),而与肿瘤切除范围、肿瘤部位、肿瘤形状、大小无关(P>0.05)。结论 MMP-9在肿瘤血管形成、恶性转化和浸润、瘤周水肿等方面起着重要作用。检测脑膜瘤MMP-9的表达对进一步了解脑膜瘤生物学行为和判断预后有重要价值。     

人脑膜瘤组织Slit2、Robo1的表达与术后复发的关系

目的 探讨人脑膜瘤Slit、Robo的表达与术后复发的关系。方法 收集2016年1月至2021年4月手术切除的脑膜瘤104例,另选取颅脑损伤内减压术切除的非肿瘤脑组织50例（对照组）,用免疫组织化学染色法检测Slit2、Robo1的表达水平。术后随访1年,判断肿瘤复发情况。结果 104例中,术后1年复发22例,复发率为21.15%。脑膜瘤组织Slit2低表达率[37.50%(39/104)]明显低于对照组[70.00%(35/50);P<0.05]。脑膜瘤组织Robo1高表达率[59.61%(62/104)]明显高于对照组[34.00%(17/50);P<0.05]。多因素logsitic回归分析显示,Slit2低表达、Robo1高表达是脑膜瘤术后复发的独立危险因素（P<0.05）。结论 脑膜瘤组织Slit2呈低表达,而Robo1呈高表达,二者均与术后复发有关。     

人脑胶质瘤病理分级与Ⅰ型纤溶酶原激活物抑制物关系的研究

目的观察I型纤溶酶原激活物抑制物（PAI－1）在人脑胶质瘤中的表达特征，研究其与胶质瘤病理分级的关系及其对胶质瘤恶性生长的调控作用，方法用抗PAI－1单克隆抗体对57例不同恶性程度的星形细胞瘤、13例良性脑膜瘤和10例正常脑组织进行免疫组织化学染色和半定量分析。结果胶质瘤恶性程度越高，PAI－1的表达程度越高。良性脑膜瘤与低度恶性胶质瘤表达程度均较低，正常脑组织未见表达、PAI－1的阳性染色主要集中于血管，坏死灶周围的PAI－1阳性血管更为集中，结论PAI－1在对抗肿瘤尿激酶所引起的肿瘤血管组织和肿瘤基质的自身降解及胶质瘤新生血管形成起重要作用。在肿瘤坏死灶周围PAI－1表达增强可能是机体防止肿瘤无限制迅速生长的防御机制．     

脑膜瘤瘤周硬膜组织蛋白酶D表达与肿瘤复发的关系

目的对组织蛋白酶D(cathepsin D)在脑膜瘤及瘤周硬膜中的表达进行研究,并探讨其在Simpson Ⅰ级切除脑膜瘤术后复发中的可能临床意义.方法临床上行Simpson Ⅰ级切除的脑膜瘤51例,术中分别取标本:肿瘤组织51例,瘤周肿瘤侵犯的硬膜组织(A组)44例,瘤周术中肉眼/镜下认为正常的硬膜组织(B组)51例,距瘤缘至少大于6 cm的正常硬膜组织(C组)15例.利用免疫组织化学方法检测各组标本的cathepsin D、增殖细胞核抗原(PCNA)表达.结果Cathepsin D在脑膜瘤组织中的表达与肿瘤的分级相关,在A组、B组、C组硬膜中的表达值分别为0.1366±0.0431、0.1149±0.0239、0.0789±0.0211,各组之间比较有显著性差异.Cathepsin D和PCNA的表达呈正相关.结论Cathepsin D可作为脑膜瘤复发的预测指标之一.脑膜瘤Simpson Ⅰ级切除后瘤周肉眼/镜下认为正常的硬膜组织在分子蛋白水平已有肿瘤细胞的残存或浸润,是术后复发的原因之一,Simpson 0级切除值得临床推荐.     

磁共振弥散张量成像在脑膜瘤诊断中的应用研究

目的探讨磁共振弥散张量成像在诊断脑膜瘤中的应用价值。方法选取30例脑膜瘤的患者为研究对象,采用Siemens Sonata 1.5T型磁共振扫描仪对其进行磁共振弥散张量成像检查,比较良性脑膜瘤、恶性脑膜瘤内不同部位及组间相应部位ADC值、FA值。结果Ⅰ级脑膜瘤患者中脑膜上皮细胞型10例,纤维型7例,沙粒体型2例,过渡型3例,微囊型1例,化生型1例,血管瘤型1例;良性脑膜瘤瘤周水肿ADC值高于肿瘤实质及瘤周白质,三者比较差异有统计学意义（P〈0.05）;良性脑膜瘤瘤周白质FA值高于肿瘤实质及瘤周水肿,其中瘤周白质FA值与肿瘤实质FA值比较和瘤周白质FA值与瘤周水肿FA值比较差异均有统计学意义（P〈0.05）;良性脑膜瘤与恶性脑膜瘤肿瘤实质ADC值及瘤周白质ADC值比较差异均有统计学意义（P〈0.05）。结论磁共振弥散张量成像能用于诊断脑膜瘤的恶性程度,在区别脑膜瘤的具体部位方面具有很高的应用价值,值得临床推广应用。     

miR-497对恶性脑膜瘤细胞增殖的影响

目的 探讨miR-497对恶性脑膜瘤细胞增殖的影响及作用机制.方法 收集2019年1～9月手术切除的女性脑膜瘤组织标本10例,其中恶性脑膜瘤5例(WHO分级Ⅲ级),良性脑膜瘤5例(WHO分级Ⅰ级),采用RNA-seq法和qRT-PCR检测脂肪酸合成酶(FASN)mRNA和miR-497表达水平.体外培养恶性脑膜瘤细胞株...     

非典型性脑膜瘤与良性脑膜瘤MRI征象的对比分析

目的 对比分析非典型性脑膜瘤与良性脑膜瘤的MRI征象特点,提高对非典型性脑膜瘤的认识。方法 回顾性分析经病理证实的37例非典型性脑膜瘤与288例良性脑膜瘤的MRI征象。结果 非典型性脑膜瘤直径>6.5 cm比例、肿瘤呈分叶型比例、瘤脑界面不清晰比例、重度瘤周水肿比例、邻近骨质改变比例均明显高于良性脑膜瘤（P<0.05）。多因素Logistic回归分析显示,肿瘤较大及瘤脑界面不清晰为非典型性脑膜瘤的可能性显著增加,肿瘤大小每增加1.5 cm,非典型性脑膜瘤的概率是良性脑膜瘤的1.507倍,瘤脑界面不清晰为非典型性脑膜瘤的概率是良性脑膜瘤的2.605倍。结论 肿瘤大小及瘤脑界面对于非典型性脑膜瘤与良性脑膜瘤的鉴别诊断具有重要价值。     

人脑肿瘤已糖激酶的活性测定

测定10例良性胶质瘤、18例恶性胶质瘤、12例良性脑膜瘤和1例恶性脑膜瘤的溶解性和总体己糖激酶(Hexokinase,HK)活性,以18例正常脑组织作对照.结果表明:良性与恶性脑瘤的HK活性明显低于正常脑组织(P<0.01).良性脑瘤的总体HK活性明显低于恶性脑瘤(P<0.05),脑膜瘤的HK活性明显低于良性及恶性胶质瘤(P<0.05,P相似文献   

Do aggressive imaging features correlate with advanced histopathological grade in meningiomas?

Atypical and malignant meningiomas are more likely to recur than benign meningiomas. We aimed to distinguish atypical and malignant meningiomas from benign meningiomas based on imaging findings. Between 2004 and 2007, a total of 75 patients with resected intracranial meningiomas were retrospectively reviewed. Histopathological grades were assigned as benign and atypical/malignant meningiomas according to the World Health Organization (WHO) classification. All patients received preoperative CT scans and MRI studies. Six aggressive imaging features were evaluated and compared between the two groups: (i) intratumoral cystic change; (ii) hyperostosis of the adjacent skull; (iii) bony destruction; (iv) extracranial tumor extension through the skull base foramina; (v) arterial encasement; and (vi) peritumoral brain edema. There were 59 benign and 16 atypical/malignant meningiomas. Only intratumoral cystic change and extracranial tumor extension through the skull base foramina were more prevalent in atypical/malignant meningiomas (p = 0.001). Hence, these two imaging features might be potential markers of atypical/malignant meningiomas.     

Diagnostic validity of the Ki-67 labeling index using the MIB-1 monoclonal antibody in the grading of meningiomas

BACKGROUND: About 10% of meningiomas behave aggressively and are graded atypical or malignant with important therapeutic and prognostic implications. Routine histological parameters are inconsistent in the assessment of their aggressive behavior. AIMS: The aim of this study was to find a threshold level of the MIB-1 labeling index (MIB-1 LI) with the highest diagnostic validity in predicting histological atypia in a meningioma. SETTING AND DESIGN: This was a retrospective study of all atypical and malignant meningiomas diagnosed at our center between January 1995 and June 2000 and which were identified from the General Pathology Registry. MATERIAL AND METHODS: These meningiomas were assessed histologically with respect to the individual criteria of atypia. They were categorized according to the WHO 2000 classification as benign, atypical and anaplastic meningiomas, WHO Grades I, II and III respectively and by immunohistochemical analysis using the MIB-1 monoclonal antibody. STATISTICAL ANALYSIS: The diagnostically useful cut-off level for the prediction of atypia was estimated by calculating the sensitivity and specificity of the MIB-1 LI at various levels and a receiver operated characteristic (ROC) analysis was performed. The correlation between the individual histological parameters was studied and the MIB-1 LI was obtained using Fisher's exact test. RESULTS: Of the 40 meningiomas studied 21 were benign, 16 atypical and 3 anaplastic. Atypical tumors had a higher MIB-1 LI than benign tumors, with diagnostic validity highest at a threshold of 7%, with a sensitivity of 0.86 and a specificity of 0.93, giving a likelihood ratio of 17. The MIB-1 LI correlated well with mitotic activity and the other individual criteria in the WHO 2000 definition of atypia in a meningioma. MIB-1 LI did not, however, correlate well with brain invasion. CONCLUSION: The MIB-1 LI has the highest validity in the diagnosis of atypia in meningiomas at a threshold level of 7%. The MIB-1 LI used in conjunction with histological features can help in making a recommendation regarding potentially aggressive behavior in meningiomas.     

Evaluation of meningioma aggressiveness by (99m)Tc-Tetrofosmin SPECT

OBJECTIVES: Although meningiomas usually have a benign clinical course, atypical and malignant types of this brain tumor are associated with high recurrence rates and poor outcome; thus, DNA ploidy and S-phase -- as determined by DNA flow cytometry -- are useful indicators of their biological behavior. Brain single-photon emission computed tomography (SPECT) has been suggested as a potentially useful modality for the metabolic assessment of various brain tumors. This study evaluated whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake correlates with meningioma proliferative activity, as assessed by flow cytometry analysis. PATIENTS AND METHODS: Ten consecutive patients (3 males, 7 females, mean age 64.6 years) with a diagnosis of a symptomatic intracranial meningioma, planned to undergo surgery, were studied. Brain SPECT by (99m)Tc-TF was performed within a week prior to surgical excision and flow cytometric analysis was performed in the excised tissue. Tumoral radiotracer accumulation was first assessed visually. Semiquantitative image analysis was also performed, by calculating the lesion-to-normal (L/N) uptake ratio. RESULTS: Benign meningiomas were diagnosed in 8/10 cases, the remaining 2/10 patients had anaplastic lesions. DNA aneuploidy was found in 2 lesions, the remaining tumors were diploid. There was a significant correlation between tracer uptake and the percentage of the cell fraction on S-phase (r=0.733, P=0.05). There was also a positive correlation between tracer uptake and the level of aneuploidy and tumor grade. CONCLUSION: These results imply that (99m)Tc-TF brain SPECT may have the ability to discriminate benign meningiomas from malignant meningiomas pre-operatively, the tracer uptake being a likely indicator of their proliferative activity.     

脑膜瘤组织病理异型性与其侵袭行为的关系

目的探讨脑膜瘤组织病理学的异型性改变与其侵袭行为的关系。方法对我院收治的103例脑膜瘤患者的临床资料进行回顾性分析,用半定量的方法评估每例肿瘤病理标本的组织病理异型性特征和侵袭性特征;并根据异型性特征和WHO脑膜瘤分类标准(2007)对脑膜瘤进行分类;分析脑膜瘤异型性特征和侵袭性特征的相关性及不同类型脑膜瘤侵袭性特征的差异。结果脑膜瘤的组织病理的异型性与侵袭性呈非线性正相关(r=0.548,P<0.01)。本组103例脑膜瘤,49例完全良性脑膜瘤,42例为临界良性脑膜瘤,12例为非良性脑膜瘤。临界性良性和非良性脑膜瘤的总侵袭率均明显高于完全良性脑膜瘤(P<0.01)。结论脑膜瘤的侵袭性随着组织异型性程度增加而增强,少数良性脑膜瘤也具有高侵袭性。     

Loss of tumor suppressor in lung cancer-1 (TSLC1) expression in meningioma correlates with increased malignancy grade and reduced patient survival

Meningiomas represent the second most common central nervous system tumor affecting adults. Two of the most frequent early events in meningioma tumorigenesis involve loss of expression of the neurofibromatosis 2 (NF2) and 4.1B genes. Recently, 4.1B was shown to interact with the tumor suppressor in lung cancer-1 (TSLC1) protein, prompting us to examine the expression of TSLC1 in meningiomas. We developed specific anti-TSLC1 antibodies to examine TSLC1 expression in normal human leptomeninges, human meningioma cell lines, and human meningiomas of different pathological grades by Western blot (n = 10) and immunohistochemistry (n = 123). Whereas TSLC1 was expressed in normal human leptomeninges by immunohistochemistry, TSLC1 expression was absent in 3 human malignant meningioma cell lines and markedly reduced or absent in 30% of benign meningiomas by Western blot. Restoration of TSLC1 expression in a TSLC1-deficient human meningioma cell line resulted in reduced cell proliferation. In a series of 123 meningiomas (98 adult and 25 pediatric), TSLC1 expression was absent in 48% of benign (WHO grade I), 69% of atypical (grade II), and 85% of anaplastic (grade III) meningiomas. Moreover, TSLC1 loss was associated with decreased patient survival, within the overall group, and in the atypical meningiomas. Collectively, these results suggest that TSLC1 plays an important role in meningioma pathogenesis.     

MMP-9、TIMP-1及其mRNA在脑膜瘤中的表达

目的探讨基质金属蛋白酶-9（MMP-9）、MMP-1组织抑制剂（TIMP-1）以及MMP-9 mRNA、TIMP-1 mRNA在脑膜瘤中的表达及其与脑膜瘤侵袭性的关系。方法采用免疫组化技术法测定手术切除的70例不同组织学类型脑膜瘤标本中MMP-9及TIMP-1的蛋白表达，并用原位杂交技术检测在不同组织类型脑膜瘤中MMP-9、TIMP-1基因在转录水平的表达，并测量其吸光度比值进行对比。结果MMP-9和TIMP-1在良性脑膜瘤中的阳性表达率分别为35.00％和52.50％，在恶性脑膜瘤中的阳性表达率分别为76.67％和53.33％。MMP-9在恶性脑膜瘤和良性脑膜瘤中的表达存在显著性差异（P〈0.05），而TIMP-1在二者之间差异无显著性（P〉0.05），但MMP-9 mRNA及TIMP-1 mRNA的表达在不同组织学类型脑膜瘤中存在显著性差异（P〈0.05）。结论MMP-9与脑膜瘤的生物学特性相关，促进脑膜瘤的侵袭性生长，其表达在基因转录水平已经上调，MMP-9和TIMP-1表达的失衡与脑膜瘤的恶性程度和侵袭能力相关，MMP-9、TIMP-1基因参与了脑膜瘤的发展过程，与脑膜瘤的生物学行为有关。