脑肿瘤中P53基因突变与突变型P53蛋白表达的研究

采用聚合酶链反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）法对４１例脑肿瘤进行Ｐ５３基因突变的检测，并与抗突变型Ｐ５３蛋白单抗的免疫组化染色结果相对照，结果显示脑肿瘤中Ｐ５３基因突变率为３４．１％（１４／４１），胶质瘤为２８％（１０／３６）。Ｐ５３基因突变与突变型Ｐ５３蛋白表达具有高度一致性，且二者均与脑肿瘤的分化程度有关。Ｐ５３基因突变及蛋白的表达不仅出现在高恶度胶质瘤及转移癌，而且可出现在低恶度胶质瘤中，表明Ｐ５３基因的突变在脑瘤的发生、发展过程中起重要作用。     

人脑瘤增殖特性的研究──核仁组织区染色及Ki－67免疫染色

利用Ｋｉ－６７免疫染色及ＡｇＮＯＲ嗜银染色对６例正常脑组织、４４例脑肿瘤及４个恶性胶质瘤体外细胞系的增殖活性进行检测，结果发现Ｋｉ－６７ＬＩ及ＡｇＮＯＲ平均计数都与肿瘤的病理组织学类型及分级有明显关系；且Ｋｉ－６７ＬＩ与ＡｇＮｏＲ平均计数有显著相关性（ｒ＝０．７３，Ｐ＜０．００５）。我们结果提示应用Ｋｉ－６７单抗及ＡｇＮＯＲ染色估价脑肿瘤增殖活性是一项简便、快速而可靠的技术，它提供了较组织学诊断更加精确的脑肿瘤增殖能力的信息，是对病理学诊断重要的补充和参考。     

人脑瘤增殖特性的研究—核仁组织区染色及Ki—67免疫染色

利用Ｋｉ－６７免疫染色及ＡｇＮＯＲ嗜银染色对６例正常脑组织、４４例脑肿瘤及４个恶性胶质瘤体外细胞系的增殖活性进行检测，结果发现Ｋｉ－６７ＬＩ及ＡｇＮＯＲ平均计数都与肿瘤的病理组织学类型及分级有明显关系；且Ｋｉ－６７与ＡｇＮＯＲ平均计数有显著相关性（ｒ＝０．７３，Ｐ＜０．００５）。我们结果提示应用Ｋｉ－６７单抗及ＡｇＮＯＲ染色估价脑肿瘤增殖活性是一项简便、快速而可靠的技术，它提供了较组织学诊断更加精     

P27蛋白和Ki-67抗原在人脑星形细胞肿瘤中的表达及其意义

目的 研究Ｐ２７蛋白及Ｋｉ－６７抗原在人脑星形细胞肿瘤中的表达情况以及它们之间的相互关系。方法 Ｓ－Ｐ免疫组化方法。结果 （１）Ｐ２７在星形细胞肿瘤中的表达程度（ＬＩ ｍｅａｎ＝２７．４％）显著低于非肿瘤脑组织（ＬＩ ｍｅａｎ＝６８．８％）而且其表达强度随肿瘤恶性程度增高而下降。（２）Ｐ２７与Ｋｉ－６７的表达呈显著负相关（ｒ＝－０．８６，Ｐ〈０．０１）。结论 Ｐ２７蛋白表达的制失可能与脑星形细胞肿     

人脑肿瘤转化生长因子β_2基因表达与其增殖活性相关性研究

目的探讨人脑肿瘤转化生长因子β２（ＴＧＦβ２）基因表达与其恶性进展及增殖活性的相关性。方法采用Ｎｏｒｔｈｅｒｎ杂交、免疫组化和Ｗｅｓｔｅｒｎ杂交法检测了５０例胶质瘤、３０例脑膜瘤、３个恶性胶质瘤体外细胞系和８例正常脑组织ＴＧＦβ２的表达水平。用Ｋｉ６７标记指数（Ｋｉ６７ＬＩ）检测肿瘤增殖活性。结果正常脑组织无ＴＧＦβ２表达，而脑肿瘤均表达２８ｋｂ和／或５１ｋｂＴＧＦβ２ｍＲＮＡ片段和约２５ｋｄ及３０ｋｄ的蛋白；其在胶质瘤中的表达显著高于脑膜瘤，而低恶度胶质瘤（Ⅰ、Ⅱ）、Ⅲ、Ⅳ级胶质瘤、体外细胞系四者表达水平也有显著性差异；ＴＧＦβ２表达水平与Ｋｉ６７ＬＩ呈正相关。结论ＴＧＦβ２表达水平有随肿瘤增殖活性增高而升高的趋势，提示其可能为胶质瘤恶性进展的重要原因之一。且有可能作为基因治疗的候选基因     

胶质瘤bFGF基因表达与增殖活性的相关性研究

目的探讨碱性成纤维细胞生长因子（ｂＦＧＦ）的异常表达与胶质瘤的恶性程度和增殖活性的关系。方法采用Ｎｏｒｔｈｅｒｎ杂交和免疫组化法对５７例人脑胶质瘤进行ｂＦＧＦ基因表达及Ｋｉ－６７标记指数检测及相关性分析。结果各组胶质瘤均有ｂＦＧＦｍＲＮＡ表达，且表达水平以恶性胶质瘤为高。Ｋｉ－６７标记指数在胶质瘤中升高显著。ｂＦＧＦｍＲＮＡ表达水平与胶质瘤恶性度及Ｋｉ－６７标记指数呈正相关。结论ｂＦＧＦ与胶质瘤的恶性进展有关，可作为判定胶质瘤恶性度的指标之一。     

p53,CerbB—2和PCNA在脑胶质瘤中表达的意义及其 …

目的 研究７６例脑质瘤的ｐ５３ＣｅｒｂＢ－２和ＰＣＮＡ表达意义及其相关性。方法 应用ＳＰ微波免疫组化技术和统计学分析。结果 （１）在７６例脑胶质瘤组织中；ｐ５３，ＣｅｒｂＢ－２和ＰＣＮＡ的阳性表达率分别是４４．７４％（３４／７６），３４．２１％（２６／７６）和８０．２６％（６１／７６）。（２）ｐ５３的表达强度与胶质瘤的组织学类型和恶性程度呈显著正相关（Ｐ〈０．０１）。（３）ｐ５３ＣｅｒｂＢ－２和Ｐ     

抗CD3-抗胶质瘤双特异抗体与IL-2协同的细胞毒性作用研究

目的：探索提高胶质瘤治疗效果的新方法。方法：以化学偶联制备抗ＣＤ３－抗胶质瘤双特异性抗体，以３Ｈ掺入法测定其与ＩＬ－２协同增强ＬＡＫ细胞对胶质瘤的细胞毒性，以ＣＤ３单抗、胶质瘤单抗、二种单抗混和物及ＲＰＭＩ１６４０作对照。结果：双特异抗体与单抗相比，能显著提高ＬＡＫ细胞对胶质瘤细胞的杀伤作用；双抗加入ＩＬ－２后，ＬＡＫ细胞毒性得到显著的提高，ＩＬ－２也能增强抗ＣＤ３单抗和ＳＺ３９单抗的细胞毒性；同时发现，来源于恶性胶质瘤患者的ＬＡＫ细胞毒性，在加入单抗、双抗和ＩＬ－２后，其细胞毒性与正常人相比，仍有显著性差异。结论：抗ＣＤ３－抗胶质瘤双特异抗体与ＩＬ－２协同可显著提高ＬＡＫ细胞对胶质瘤的细胞毒作用     

脑胶质瘤端粒酶活性特征研究

目的 研究端粒酶表达是否与胶质瘤的发生及恶性程度相关。方法 采用ＴＥＬＯＭ－ＥＲＡＳＥＰＣＲ－ＥＬＩＳＡ试剂盒（ＢＭ）对６２例胶质瘤标本端粒酶活性进行检测。评价端粒酶阳性率及活性水平。结果 １５例高恶性度胶质瘤中９例阳性，１８例中度胶质瘤中有７例阳性，２５你良性胶质瘤中有６例阳性。高恶性组胶质瘤端粒酶阳性率明显高于良性组（Ｐ〈０．０５）。大多数高端粒酶活性胶质瘤是恶性胶质瘤。另外６例髓母细胞瘤中有     

100例脑肿瘤中p53基因突变与P53蛋白积聚的研究

目的:研究不同类型脑肿瘤中的p53基因突变与P53蛋白积聚及其相关性。方法:采用聚合酶链反应-单链构象多态性(PCR-SSCP)分析及免疫组化法检测100例脑肿瘤p53基因突变及蛋白表达。结果:p53基因突变率为11%(11/100),其中高恶度胶质瘤为37.5%(6/16),低恶度胶质瘤4.3%(1/23),脑膜瘤6.9%(2/29),转移瘤40.0%(2/5)。P53蛋白表达阳性率为22%(22/100),其中高恶度胶质瘤为62.5%(10/16),低恶度胶质瘤为26.1%(6/23),脑膜瘤10.3%(3/29),转移瘤60%(3/5);其他肿瘤均未发现p53基因突变或蛋白表达。P53蛋白表达阳性的22例中伴有p53基因突变者11例,多见于高恶度肿瘤。结论:p53基因失活在脑肿瘤恶性进展过程中起重要作用。p53基因突变与P53蛋白积聚相关,但并非唯一因素。     

人脑胶质瘤中PCNA、Ki-67和Mitosin/CENP-F的表达研究

目的 检测PCNA、Ki-67和Mitosin/CENP-F在人脑胶质瘤的表达,探讨它们与胶质瘤恶性生物学行为的关系.方法 应用免疫组化S-P法检测70例不同病理分级、不同组织学分型人脑胶质瘤和24例非肿瘤脑组织中PCNA、Ki-67和Mitosin/CENP-F的表达.结果 (1)70例脑胶质瘤标本中,PCNA、Ki-67和Mitosin/CENP-F的增殖标记指数(LI)分别为(44.02±29.37)%、(17.01±17.68)%和(36.80±27023)%;对照组24例非肿瘤脑组织中Ki-67不表达,PCNA LI和Mitosin/CENP-F LI为(12.11±19.81)%和(9.06+8.27)%,两组比较具有显著差异(P<0.01).(2)PCNA、Ki-67和Mitosin/CENP-F的表达与胶质瘤患者的年龄、性别无关,与病理分级和组织学分型相关(P<0.05).结论 人脑胶质瘤中PCNA、Ki-67和Mitosin/CENP-F的LI与胶质瘤的病理分级和病理分型密切相关,均可作为判断胶质瘤恶性程度的重要指标.     

Correlation between histological grade and MIB-1 and p53 immunoreactivity in meningiomas

OBJECTIVE: Meningiomas for the most part are slow-growing benign tumors, but complete removal can be difficult and recurrence is an issue. The aim of this study was to re-evaluate tumors diagnosed as meningioma previously in our hospital, according to the latest World Health Organization classification. We also examined the relationships among parameters such as brain invasion, histological grade and Ki-67 and p53 expression in these tumors. MATERIALS AND METHODS: Meningioma biopsy specimens numbering 60 (48 grade I, 11 grade II, and 1 grade III tumors) were examined immunohistochemically using monoclonal antibodies for Ki-67 (MIB-1) and p53 protein. The MIB-1 labeling index (LI) for each tumor was calculated as a percentage based on the number of stained cells per total cells counted. The level of p53 expression in each sample was semiquantatively evaluated as < 1%, 1 - 10%, 10 - 70%, or > 70%. Any value > 1% was accepted as presence of p53 expression. RESULTS: Of the 60 meningiomas, 7 (11.7%) exhibited brain invasion. The mean MIB-1 LI values for the grade I and grade II tumors were 1.1% and 2.3%, respectively. The corresponding levels of p53 protein expression in these groups were 54.1% and 72.7%. The MIB-1 LI and the level of p53 expression in the one grade III meningioma were 6.7% and 10 - 70%, respectively. Histological grade was significantly correlated with MIB-1 LI and with p53 expression (p < 0.01 for both). Brain invasion was not correlated with histological grade, MIB-1 LI, or p53 expression. CONCLUSION: The results indicate that MIB-1 LI and p53 protein expression are good indicators of histological grade in meningioma and may be particularly valuable for distinguishing borderline atypical meningiomas. The number of cases was limited, but the findings also suggest that brain invasion is a prognostic parameter independent of grade, MIB-1 LI and p53 expression.     

LAT1表达与人脑胶质瘤病理级别、增殖和血管形成的关系

目的探讨大型氨基酸转运载体1(LAT1)在人脑胶质瘤组织中的表达水平及其与胶质瘤病理学特征、细胞增殖以及血管形成的关系。方法采用免疫组化方法检测LAT1、Ki-67和CD34在62例人脑胶质瘤组织中的表达,计算Ki-67标记指数(Ki-67 LI)和微血管密度(MVD)。结果LAT1在胶质瘤中高表达,其免疫阳性染色既定位于瘤细胞也定位于血管内皮;LAT1表达随胶质瘤病理级别升高而明显增强(P=0.000),在高恶性度胶质瘤中LAT1表达明显强于低恶性度胶质瘤(P=0.002);LAT1表达与胶质瘤Ki-67标记指数(P=0.003)和微血管密度(P=0.000)都存在明显正相关。结论 LAT1与胶质瘤的发生和发展关系密切,可能在胶质瘤的恶性增殖和血管形成中发挥重要作用。     

Ki—67表达强度对人脑胶质瘤恶性度的评价

目的 研究细胞核增殖抗原Ki-67人脑胶质瘤中的表达强度与病理分级的关系。比较Ki-67与其他评价肿瘤增殖潜能指标的优越性。方法 SP免疫组化方法对41例不同级别人脑胶质瘤细胞的Ki-67表达进行观察,评价染色强度和阳性细胞百分数与胶质瘤细胞恶性度的关系。结果 全部受检病例中对照组Ki-67均为阴性染色,全部胶质瘤标本表达阳性率达85%星形细胞瘤I级绝大部分病例为阴性染色,只存在2例阳性染色。结论 Ki-67表达与胶质瘤恶性程度相关,其表达水平不仅可以反映胶质瘤的恶性增殖潜能,亦可反映其预后,Ki-67在人脑胶质瘤中的表达可以应用于临床,作为评价胶质瘤生物学行为,选择治疗措施、预测患者生存时间的指标。     

胶质瘤中P53、EGFR、Ki-67及MGMT 的表达及临床意义

目的 探讨不同级别胶质瘤中P53、EGFR、Ki-67 及MGMT 的表达及临床意义.方法 应用免疫组织化学方法检测152 例胶质瘤中P53、EGFR、Ki-67 及MGMT 表达,统计分析上述蛋白的表达差异.结果 P53 在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性率分别为71.4%,73.1%和60.0%.95 例EGFR 阳性,其阳性表达率与染色强度均与病理级别呈正相关(P ＜0.01).Ki-67 均为阳性表达,Ki-67LI 在高级别胶质瘤中明显高于其在低级别胶质瘤中的表达水平(P ＜0.01).MGMT 阳性84 例,阴性68 例,在低级别胶质瘤和高级别胶质瘤之间的MGMT 表达无明显差异(P ＞0.05).结论 EGFR 和Ki-67 表达与肿瘤病理级别呈正相关,与胶质瘤恶性进展及预后差密切相关.P53 和MGMT 与肿瘤病理级别无明显相关性.检测有助于评估胶质瘤侵袭能力、增殖性,预测胶质瘤对放、化疗敏感性及判断分子靶向药物治疗是否有效.     

联合应用MRS和DWI对胶质瘤级别及侵袭性进行临床评估

目的探讨应用氢质子磁共振波谱成像(1H-MRS)和弥散加权成像(DWI)对判别胶质瘤级别和侵袭性的价值,为临床评估胶质瘤生物学特性并制定手术方案提供影像学支持。方法回顾性分析27例幕上胶质瘤病人的临床资料,术前行常规MRI、MRS和DWI检查,比较正常脑组织、高级别胶质瘤与低级别胶质瘤间胆碱与乙酰天门冬氨酸的比值(Cho/NAA)及胆碱与肌酸(Cho/Cr)比值、表观弥散系数(ADC)、Ki-67标记指数(Ki-67 IL)的差异性,并分析ADC与Ki-67 IL的相关性。结果与正常脑组织对比,高级别胶质瘤中Cho/NAA及Cho/Cr比值显著升高,ADC值降低(均P0.01)。与低级别胶质瘤比较,高级别胶质瘤肿瘤中Cho/NAA及Cho/Cr比值升高,ADC值降低,Ki-67 IL升高(均P0.05)。与正常脑组织比较,低级别胶质瘤中Cho/NAA、Cho/Cr值升高(均P0.05)。在高级别胶质瘤中,Ki-67 IL与ADC值负相关(r=-0.683,P0.05);而在低级别胶质瘤中,Ki-67 IL与ADC值无相关性(r=0.187,P0.05)。结论 MRS联合DWI能够在术前评价胶质瘤的恶性程度及瘤细胞侵袭性,对胶质瘤手术治疗有重要意义。     

The relationship between Ki-67 labeling and mitotic index in gliomas and meningiomas: demonstration of the variability of the intermitotic cycle time

Summary The monoclonal antibody (mAb) Ki-67 is a marker for the growth fraction (GF) of tumor cells. The exact relationship between the Ki-67 labeling index (LI) and the conventional diagnostic criterion of the proliferative activity of brain tumors, the mitotic index (MI), is unknown except for some general references. On serial frozen sections Ki-67 LI and MI were determined in nearly identical areas of 32 glioblastomas, 20 grade III astrocytomas, 21 grade II astrocytomas and 20 selected cases of meningioma. The data not only clearly showed different median values of LI and MI for the various malignancy grades, but also similar regression coefficients for each glioma type. A non-linear relationship between the two indices was found for all glioma cases with high significance and high correlation coefficient; (LI)=5.6 (MI)^0.59. This results from differing intermitotic cycle times, the variability of which can be estimated from the data given.Dedicated to Prof. Dr. Dr. W. MüllerSupported by the Verein der Freunde und Förderer der Universität Köln     

Gliomas of the optic nerve: histological, immunohistochemical (MIB-1 and p53), and MRI analysis

Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pilocytic and diffuse astrocytomas difficult. We reviewed 22 cases of optic nerve gliomas, 19 of which were pilocytic astrocytomas (PA), and 3 of which were diffuse, non-pilocytic astrocytomas. The cases were evaluated for their clinical course, radiographic appearance, histologic grade, and proliferation indices as detected by MIB-1 (Ki-67) and p53 antibodies. Of the 19 PA, 14 showed no tumor growth by magnetic resonance imaging, and had Ki-67 and p53 labeling indices (LI) of < 1%. The other 5 PA exhibited aggressive behavior manifest by marked diffuse infiltrative tumor growth causing death in 2 patients, 1 of whom was diagnosed with neurofibromatosis type 1 (immunoperoxidase and radiographs not available), and marked local growth with an average time to growth of 39.3 months, a Ki-67 LI of 2–3%, and a p53 LI of < 1% in three others. Three of the five aggressive PA histologically demonstrated a finely reticulated pattern, a pattern that appears as an exaggeration or expansion of the normal neuroglia of the optic nerve, and may simulate a diffuse low-grade astrocytoma. Two demonstrated the coarsely reticulated pattern, with the biphasic and microcystic pattern typical of PA. Three diffuse astrocytomas (2 anaplastic astrocytomas and 1 glioblastoma) originated clinically and radiographically from the optic nerve, and revealed a Ki-67 LI of 2–12%, a p53 LI of 2–8%, and an average time to growth of 8 months. We conclude that the majority of PA of the optic nerve are non-aggressive, stabilize radiographically, and have Ki-67 and p53 LI < 1%. However, a subpopulation of PA has a propensity for aggressive behavior, and are identified by a Ki-67 LI of 2–3% and a p53 LI of < 1%. Diffuse astrocytomas have both Ki-67 and p53 LI > 2%. Thus, in cases of aggressive optic nerve tumors in which the histologic review of biopsy material cannot confidently confirm the diagnosis of pilocytic or diffuse fibrillary glioma, a p53 LI of > 1% appears to favor the diagnosis of diffuse astrocytoma. Received: 18 May 1999 / Revised: 10 August 1999 / Accepted: 18 August 1999     

人脑胶质瘤中Fas及FasL的表达

目的　探讨Fas及FasL基因在人脑胶质瘤中的表达 ,与肿瘤的病理类型及恶性程度的关系。方法　应用Fas及FasL多抗和Ki 6 7单抗免疫组化染色检测 6例正常脑组织及 6 4例人脑胶质瘤。结果　Fas和FasL在胶质瘤中的总表达率分别为 83%和 75 % ,并随WHO分级升高而升高 ,与Ki 6 7LI呈正相关。Fas、FasL共同阳性率 (共表达率 )为 71% ,与肿瘤级别呈正相关。结论　脑胶质瘤中Fas及FasL表达与肿瘤病理类型及恶性程度密切相关     

microRNA-128在胶质瘤中的表达及其临床意义

目的 研究人脑胶质瘤的microRNA-128(miR-128)表达水平及IDH1突变型、MGMT、Ki-67蛋白表达与胶质瘤病理分级、预后的关系.方法 收集脑胶质瘤手术标本21例,其中病理分级低级别者13例、高级别者8例;脑外伤清除组织6例.采用实时定量PCR法检测胶质瘤标本及胶质瘤细胞株U87、人小胶质细胞株HMC...