甘油醛-3-磷酸脱氢酶与人脑胶质瘤的相关性研究

目的探讨甘油醛-3-磷酸脱氢酶在神经胶质瘤中的表达及其临床意义。方法选择1999年11月-2004年1月手术切除,经病理证实的胶质瘤标本51例(胶质瘤组)、脑膜瘤9例(脑膜瘤组)、垂体瘤5例(垂体瘤组)。根据WHO2000年分级标准,胶质瘤组Ⅱ级胶质瘤16例(星形细胞瘤13例、少突胶质细胞瘤1例、室管膜瘤1例、混合性星形-少突胶质细胞瘤1例);Ⅲ级胶质瘤17例(间变性星形细胞瘤9例、间变性少突胶质细胞瘤7例、间变性室管膜瘤1例);Ⅳ级胶质瘤18例(均为胶质母细胞瘤)。脑膜瘤组为Ⅰ级脑膜瘤6例(纤维型脑膜瘤),Ⅱ级脑膜瘤3例(非典型性脑膜瘤)。垂体瘤组中垂体生长激素/催乳素细胞腺瘤1例,垂体催乳素细胞腺瘤1例,垂体多激素细胞腺瘤3例。采用免疫组化方法检测脑肿瘤组织中甘油-3-磷酸脱氢酶的表达程度。结果(1)胶质瘤Ⅱ～Ⅳ级标本免疫组化染色均呈阳性反应,脑膜瘤、垂体瘤和正常对照组则为阴性反应。(2)不同病理分级的胶质瘤标本中甘油醛-3-磷酸脱氢酶表达水平各异,其中胶质瘤Ⅱ级者甘油醛-3-磷酸脱氢酶阳性细胞检出率为12.8%,Ⅲ级22.9%,Ⅳ级44.5%,三者间差异具有显著性意义(P<0.05);而且甘油醛-3-磷酸脱氢酶阳性细胞检出率与胶质瘤的病理分级呈线性正相关(r=0.606,P<0.05)。结论甘油醛-3-磷酸脱氢酶蛋白表达水平的增高在胶     

14-3-3蛋白在星形细胞瘤中的表达及意义

目的探讨14-3-3蛋白在星形细胞瘤中的表达与肿瘤病理分级和预后间的关系。方法采用免疫组化ABC法检测10例正常脑组织和67例确诊并有随访的人脑星形细胞瘤石蜡标本中14-3-3蛋白的表达情况。分析14-3-3蛋白的表达与肿瘤恶性程度及预后间的关系。结果在正常脑组织标本中，14-3-3蛋白主要表达于神经元胞体和突起，而在少数的胶质细胞中仅见其弱表达。绝大部分星形胶质细胞瘤中可见14-3-3蛋白阳性表达，其阳性表达率为：Ⅱ级76．5％（13／17），Ⅲ级76．2％（16／21），Ⅳ级79．3％（23／29）。不同恶性级别的星形细胞肿瘤中，14-3-3蛋白的阳性表达率无显著差别（P〉0．05），但14-3-3蛋白表达的强度和范围有随肿瘤的恶性度增高而增加的趋势（P〈0．05）。52例14-3-3蛋白阳性表达患者的生存期明显短于15例14-3-3蛋白表达阴性的患者（P〈0．01）。结论14-3-3蛋白在人脑星形细胞瘤中的表达上凋与肿瘤的恶性程度及预后相关。14-3-3蛋白有望成为星形细胞瘤基因治疗的新靶点。     

脑胶质瘤低氧诱导因子鄄1α的表达及其意义

目的探讨低氧诱导因子鄄1α在脑胶质瘤中的表达及其意义。方法60例脑胶质瘤标本中Ⅰ级11例(毛细胞型星形细胞瘤8例、脉络丛乳头状瘤2例、黏液乳头状型室管膜瘤1例);Ⅱ级20例(弥漫型星形细胞瘤11例、少突胶质细胞瘤5例、室管膜瘤2例、多形性黄色瘤型星形细胞瘤2例);Ⅲ级21例(间变性星形细胞瘤12例、间变性少突胶质细胞瘤6例、间变性室管膜瘤3例);Ⅳ级8例(均为胶质母细胞瘤)。采用免疫组织化学方法检测胶质瘤标本中低氧诱导因子鄄1α的表达变化,并与胶质瘤体积及患者年龄、性别进行统计学分析。结果(1)胶质瘤组织低氧诱导因子鄄1α表达呈阳性反应,主要位于细胞质和(或)细胞核,具有明显的异质性;肿瘤浸润边缘部的肿瘤细胞表达明显增强;而阴性对照标本和10例对照脑组织标本则无表达。胶质瘤组织中低氧诱导因子鄄1α阳性表达率为71.67%(43/60),其中Ⅰ级为27.27%(3/11),Ⅱ级70.00%(14/20),Ⅲ级85.71%(18/21),Ⅳ级100%(8/8)。高级别胶质瘤者低氧诱导因子鄄1α阳性表达率明显高于低级别者,不同级别间差异有高度统计学意义(χ2=15.907,P<0.01);表达强度与病理级别间呈高度正相关(rs=0.480,P<0.01)。(2)低氧诱导因子鄄1α表达与患者年龄、性别及原发肿瘤体积的大小等均无相关性(均P>0.05)。结论脑胶质瘤低氧诱导因子鄄1α的表达强弱与肿瘤病理分级相关。     

14-3-3β在人脑星形细胞瘤中的表达及意义

目的探讨14-3-3β在人脑星形细胞瘤中表达与肿瘤病理分级的关系。方法采用免疫组化法检测14-3-3β亚型在80例人脑星形细胞瘤和10例正常脑组织标本中的表达水平。结果在正常脑组织中，14-3-3蛋白6亚型只表达于神经元胞体和突起，在胶质细胞中未见表达。母亚型在人脑星形细胞瘤的表达阳性率及免疫反应评分（IRS）分别为60％、1．86±1．83。Ⅰ～Ⅳ级脑星形细胞瘤中β亚型表达阳性率分别为40％（8／20）、50％（10／20）、70％（14／20）和80％（16／20）。Ⅰ～Ⅳ级脑星形细胞瘤中β亚型IRS分别为0．88．4±0．27、1．15±0．28、2．19±0．37和3．23±0．47。不同恶性级别的脑星形细胞瘤中，14．3-3蛋白β亚型的阳性表达率无显著差异，但其IRS有显著差异（P〈0．05）。结论14-3-3β在人脑星形细胞瘤中高表达，且随着星形细胞瘤病理级别的增高而表达增强，14-3-3蛋白β亚型在脑星形细胞瘤的发生过程中具有重要作用。     

脑胶质瘤低氧诱导因子-1α的表达及其意义

目的 探讨低氧诱导因子-1α在脑胶质瘤中的表达及其意义。方法60例脑胶质瘤标本中Ⅰ级11例（毛细胞型星形细胞瘤8例、脉络丛乳头状瘤2例、黏液乳头状型室管膜瘤1例）；Ⅱ级20例（弥漫型星形细胞瘤11例、少突胶质细胞瘤5例、室管膜瘤2例、多形性黄色瘤型星形细胞瘤2例）；Ⅲ级21例（间变性星形细胞瘤12例、间变性少突胶质细胞瘤6例、间变性室管膜瘤3例）；Ⅳ级8例（均为胶质母细胞瘤）。采用免疫组织化学方法检测胶质瘤标本中低氧诱导因子-1α的表达变化，并与胶质瘤体积及患者年龄、性别进行统计学分析。结果（1）胶质瘤组织低氧诱导因子-1α表达呈阳性反应，主要位于细胞质和（或）细胞核，具有明显的异质性；肿瘤浸润边缘部的肿瘤细胞表达明显增强；而阴性对照标本和10例对照脑组织标本则无表达。胶质瘤组织中低氧诱导因子-1α阳性表达率为71．67％（43／60），其中Ⅰ级为27．27％（3／11），Ⅱ级70．00％（14／20），Ⅲ级85．71％（18／21），Ⅳ级100％（8／8）。高级别胶质瘤者低氧诱导因子-1α阳性表达率明显高于低级别者，不同级别间差异有高度统计学意义（X^2=15．907，P〈0．01）；表达强度与病理级别间呈高度正相关（rn=0．480，P〈0．01）。（2）低氧诱导因子-1α表达与患者年龄、性别及原发肿瘤体积的大小等均无相关性（均P〉0．05）。结论脑胶质瘤低氧诱导因子-1α的表达强弱与肿瘤病理分级相关。     

恶性胶质瘤组织中Bcl-xL mRNA和蛋白的表达及其与临床病理的关系

目的探讨恶性胶质瘤组织中bcl-xLmRNA和蛋白的表达及其与临床组织病理的关系。方法用免疫组化染色SP法和RT-PCR分别检测44例间变星形细胞瘤、45例胶质母细胞瘤和26例Ⅰ级星形细胞瘤组织中bcl-xLmRNA和蛋白的表达。结果bcl-xL蛋白表达的阳性率在间变星形细胞瘤中为86.40%,胶质母细胞瘤中为91.1%,与Ⅰ级星形细胞瘤的38.5%相比,差异显著(P<0.01)。bcl-xLmRNA相对含量在间变星形细胞瘤和胶质母细胞瘤中分别为0.89±0.26和0.93±0.21,与Ⅰ级星形细胞瘤的0.63±0.23相比,差异显著(P<0.01)。结论bcl-xLmRNA和蛋白表达与胶质瘤临床病理分级呈显著正相关,其高表达可能与胶质瘤的恶性进展密切相关。     

MR扩散加权成像对脑胶质瘤病理分级的临床研究

目的 探讨MR扩散加权成像对脑胶质瘤病理分级的临床应用价值.方法 选择经病理证实的30例脑胶质瘤患者入组研究,患者行MR扩散加权成像,测量肿瘤实质的表观扩散系数(ADC)、相对表观扩散系数(rADC)值,并进行统计学分析.结果 30例脑胶质瘤中低级别胶质瘤14例(Ⅰ级1例,为毛细胞型星形细胞瘤;Ⅱ级13例,其中星形细胞瘤11例.1例为术后复发,另室管膜瘤、少突胶质细胞瘤各一例),高级别胶质瘤16例(Ⅲ级11例,均为间变性星形细胞瘤,1例为术后复发;Ⅳ级5例,其中胶质母细胞瘤4例,室管膜瘤1例).低级别胶质瘤的ADC、rADC均值分别为(1.36±0.16)×10-3 mm2/s、1.76±0.23,高级别胶质瘤的ADC、rADC均值分别为(1.08±0.10)×10-3mm2/s、1.36±0.16,高级别与低级别胶质瘤的ADC、rADC均值比较差异有统计学意义(P<0.05).以低级别胶质瘤肿瘤实质ADC、rADC值的下限1.20×10.3mm2/s、1.53作为判断阈值,本组中诊断正确率分别为86.7%、83.3%.结论 ADC、rADC值对脑胶质瘤病理分级的诊断有较高的准确性.     

不同放射敏感性胶质瘤中ATM蛋白、NF-κB表达及相关性研究

目的探讨ATM蛋白、NF-κB在不同放射敏感性胶质瘤中的表达及相互关系。方法应用免疫组织化学SABC法检测ATM蛋白、NF-κB在儿例髓母细胞瘤,12例室管膜瘤,17例少枝胶质细胞瘤,低级别(Ⅰ～Ⅱ级)及高级别星形细胞瘤(Ⅲ～Ⅳ级)各21例和5例正常脑组织中的表达。结果正常脑组织中均未见阳性表达。ATM蛋白、NF-κB在82例不同组织类型胶质瘤中的阳性表达率分别为32.9%、48.8%,二者阳性和阴性同时表达者分别为25.6%、36.5%;ATM蛋白在多形性胶质母细胞瘤表达率最高,在髓母细胞瘤和低级别星形细胞瘤表达较低,髓母细胞瘤中平均光密度值与其他各组均有显著性差异(P<0.05)。NF-κB表达率在髓母细胞瘤、室管膜瘤、少枝胶质细胞瘤、低及高级别星形细胞瘤、多形性胶质母细胞瘤中里依次上升趋势。结论ATM蛋白与NF-κB存在相关关系,它们的表达水平与胶质瘤的不同放射敏感性具有相关性。     

胶质瘤放射敏感性与EGFR表达关系的探讨

目的探讨EGFR的表达水平与胶质瘤放射敏感性的关系。方法应用免疫组织化学SABC法检测EGFR在5例正常脑组织,2种胶质瘤细胞系及82例不同放射敏感性胶质瘤中的表达。结果EGFR在正常脑组织未见表达,在两种胶质瘤细胞系表达率为100%。EGFR在髓母细胞瘤、室管膜瘤、少枝胶质细胞瘤、低(Ⅰ~Ⅱ级)及高级别(Ⅲ~Ⅳ级)星形细胞瘤、多形性胶质母细胞瘤的表达率呈依次上升趋势。髓母细胞瘤表达率最低,与其他各组均有显著性差异(P<0.05)。结论EGFR表达水平与胶质瘤的不同放射敏感性可能相关。     

热休克蛋白27在人脑星形胶质细胞瘤中的表达及意义

目的检测热休克蛋白27(heat shock protein 27,HSP27)在人脑星形胶质细胞瘤组织中的表达,探讨其在胶质瘤细胞中的作用。方法选择人脑星形胶质细胞瘤组织,采用免疫组化检测热休克蛋白27的表达水平。结果 HSP27在人脑星形胶质细胞瘤组织中的阳性表达率较瘤旁组织和正常脑组织明显增高,HSP27的表达量随着星形胶质细胞的恶变有所增加。结论 HSP27的阳性表达率与瘤细胞含量的多少有关,与临床病理特征无关。     

Trk A, B, and C are commonly expressed in human astrocytes and astrocytic gliomas but not by human oligodendrocytes and oligodendroglioma

Neurotrophins regulate the proliferation and differentiation of neurons in the central nervous system via a family of specialized receptors, including TrkA, TrkB, and TrkC. As little is known about their expression or potential role in human glial tissues and glial tumors, we undertook an immunohistochemical analysis of human glia, glioma tissues and cell cultures of glial tumors to characterize the expression of Trk family members (full-length TrkA, TrkB, the truncated form of TrkB, and TrkC). In normal human brain Trk A, B, and C immunoreactivity was found in neurons and some weak staining was also seen astrocytes. No Trk expression was seen on oligodendrocytes. Strong reactivity was seen in reactive astrocytes in a glial scar. In a total of 34 glioma tissue specimens, which included 16 astrocytic tumors (4 low-grade astrocytomas and 12 glioblastomas multiforme) and 15 oligodendrogliomas (8 low-grade and 7 anaplastic) as well as 3 oligoastrocytomas (WHO grade II), TrkA, B, and C immunoreactivity was observed exclusively in specimens from astrocytic gliomas (16/16), but not in any of the oligodendrocytic gliomas (0/15). In the oligoastrocytomas, staining was restricted to the astrocytic component. In the astrocytoma and oligodendroglioma specimens, Trk A, B, and C immunoreactivity was also seen in the surrounding reactive astrocytes. Trk expression was independent of age, sex or histological grade of the investigated tumors. In six primary cell cultures, one derived from human astrocytes and five established from malignant astrocytomas, only TrkA immunoreactivity could be detected, while TrkB (both full-length and truncated isoforms) and TrkC were absent. The TrkA expression in primary cell cultures decreased with continuous cell passaging, and no Trk could be detected in established cell lines derived from glioblastoma. In conclusion, our data suggest that in human glial tissues Trk A, B, and C may be expressed in a lineage-restricted manner, thereby distinguishing between astrocytes and oligodendrocytes in a marker-like fashion. Trk expression, like GFAP expression appears to be increased in activated (reactive)/ neoplastic astrocytes. Received: 15 January 1998 / Revised, accepted: 27 March 1998     

Expression of the placental form of glutathione S-transferase in pediatric gliomas

Expression of the human placental form of glutathione S-transferase (GST-) in pediatric gliomas, consisting of three pilocytic astrocytomas (grade 1), two fibrillary astrocytomas (grade 2), three anaplastic astrocytomas (grade 3), and one glioblastoma multiforme (grade 4), were investigated by immunohistochemical methods. Western blot analysis for GST- using proteins extracted from formalin-fixed and paraffin-embedded glioma specimens was performed and compared with the results of immunohistochemistry. Both the immunohistochemical examination and the Western blot analysis of pediatric gliomas revealed that malignant gliomas such as anaplastic astrocytoma and glioblastoma had strong expression of GST- while benign gliomas showed weak GST- expression.     

Analysis of Isocitrate Dehydrogenase 1 Mutation in 97 Patients with Glioma

The objective of this study is to investigate the expression and significance of isocitrate dehydrogenase 1 (IDH1) mutation in different subtypes of human gliomas. Direct DNA sequencing, western blot, and immunohistochemistry were used to detect IDH1 mutation and IDH1 gene expression levels in 97 cases of glioma and 9 cases of other CNS tumors. IDH1 mutation was heterozygous, with wild-type arginine 132 replaced by histidine (R132H). Expression in different glioma subtypes was (1) 0 out if 5 in pilocytic astrocytoma; (2) 15 out of 22 in diffuse astrocytoma, 6 out of 9 in oligodendroglioma, 4 out of 6 in oligoastrocytoma, and 0 out of 4 in ependymoma; (3) 11 out of 19 in anaplastic astrocytoma, 4 out of 7 in anaplastic oligodendroglioma, 3 out of 4 in anaplastic oligoastrocytoma, and 0 out of 3 in anaplastic ependymoma; and (4) 1 out of 6 in primary glioblastoma, 8 out of 10 in secondary glioblastoma, and 0 out of 2 in medulloblastoma. IDH1 mutation is a somatic mutation that is found only in some glioma subtypes. It can be used as a molecular marker for glioma subtypes. For example, it can be used to distinguish primary glioblastoma from secondary glioblastoma, combining TP53 mutation and loss of heterozygosity involving 1p/19q. It can also be used as a marker for some gliomas. For example, it can be used to distinguish pilocytic astrocytoma from diffuse astrocytoma, combining detected BRAF proto-oncogene mutations.     

Olig-2在人脑胶质细胞瘤中的表达及临床意义

目的研究少突胶质细胞转录因子-2（Olig-2）在人脑胶质细胞瘤组织中的表达,并探讨其临床意义。方法采用免疫组化sP法和蛋门印迹技术（Westernblot）,检测96例脑胶质细胞瘤患者的手术标本,WHO分类：Ⅰ级26例,Ⅱ级28例,Ⅲ级20例,Ⅳ级22例;组织学分类：巨细胞星形胶质细胞瘤26例,少突胶质细胞瘤28例,间变性星形胶质细胞瘤20例,多形胶质母细胞瘤10例,髓母细胞瘤12例和10例颅脑损伤内减压脑组织标本中Olig-2蛋白的表达水平：结果免疫组化结果表明：巨细胞星形胶质细胞瘤阳性表达牢为23．08％（6／26）,少突胶质细胞瘤阳性表达率为82．14％（23／28）,间变性星形胶质细胞瘤阳性表达率为40．00％（8／20）,多形胶质母细胞瘤阳性表达率为30．00％（3／10）,髓母细胞瘤阳性表达率为75．00％（9／12）和正常脑组织阳性表达率为60．00％（6／10）;Olig-2阳性率在良性（Ⅰ＋Ⅱ）和恶性（Ⅲ＋Ⅳ）中分别为53．70％（29／54）和47．62％（20／42）,统计学处理无明显差异（P〉0．05）;少突胶质细胞瘤Olig-2阳性率82．14％（23／28）和其它病理类型肿瘤阳性率38．24％（26／68）比较有明显差异（P〈0．05）;Westernblot结果显示少突胶质细胞瘤中Olig-2蛋白的表达明显高于其它类型胶质细胞瘤及正常脑组织（P〈0．05）。结论Olig-2在少突胶质细胞瘤中明显高表达,但表达水平与脑胶质细胞瘤恶性程度无明显相关,Olig-2可以作为人脑少突胶质细胞瘤与其它类型胶质细胞瘤鉴别诊断的重要标记物.