P53、PTEN、Ki-67在原发性胶质母细胞瘤和继发性胶质母细胞瘤中的表达及意义

目的探讨P53、PTEN、Ki-67蛋白在原发性和继发性胶质母细胞瘤中的表达差异及其意义。方法采用免疫组化方法检测人原发性和继发性胶质母细胞瘤标本及正常人脑组织标本中P53、PTEN和Ki-67蛋白的表达情况,并分析上述蛋白的表达差异。结果在正常脑组织标本中,PTEN蛋白阳性率为100%;P53和Ki-67均表达阴性。原发性和继发性胶质瘤标本中,P53蛋白阳性率分别为28.6%、62.5%;PTEN蛋白阳性率分别为78.5%、37.5%;Ki-67蛋白阳性率分别为35.7%、68.8%。P53和Ki-67在原发性胶质母细胞瘤与正常脑组织之间表达均有显著差异(均P0.05)。P53、PTEN和Ki-67蛋白在继发性胶质母细胞瘤和正常脑组织之间以及原发性胶质母细胞瘤和继发性胶质母细胞瘤之间表达均有显著差异(均P0.05)。结论 P53、PTEN及Ki-67蛋白在胶质母细胞瘤的发生、发展中起重要作用,联合检测三者表达可为判断不同类型胶质母细胞瘤提供依据。     

p16在星形胶质细胞瘤患者生存分析中的意义

目的探讨p16在星形胶质细胞瘤患者生存分析中的意义。方法采用免疫组化方法检测p16、Rb、细胞周期素D1(cyclinD1)及Ki-67蛋白在62例星形胶质细胞瘤中的表达,对患者进行随访,并结合临床和影像学资料进行生存分析,研究p16的预后意义。结果单因素分析表明p16阴性病例术后生存时间较阳性者明显为短(Logrank检验,P<0.001),而这种差别在卡诺夫斯基机能状态(KPS)评分<70分、复发性肿瘤、Rb和cyclinD1蛋白阴性的病例中不存在;p16不同表达强度的患者之间预后也有差别;但多因素COX模型分析显示p16不是独立的预后因子(P=0.06)。结论p16是能反映星形胶质细胞瘤恶性生物学行为的分子标志物之一,对星形胶质细胞瘤具有初步判断预后的价值,但不是独立的预后因子。     

人脑胶质母细胞瘤在不同周期时相中P16和P21的表达

目的 探讨人脑胶质母细胞瘤细胞株U-251MG在不同周期时相中P16和P21的表达。方法 采用高同步率、高收获率的细胞周期同步化方法,把U-251MG细胞同步在不同的时期,利用免疫组织化学方法检测在不同周期时相中P16、P21的表达。结果 P16在所有周期时相均有表达,而且在G_1期表达最强烈;P21在除S期以外其它周期时相均有表达,同样在G_1期表达最强烈。结论 U—251MG的细胞增殖受细胞周期负性调控因子P16和P21的影响,但它们有各不相同的作用时相和机制。     

P16蛋白在人脑髓母细胞瘤中的表达及意义

目的：研究Ｐ１６蛋白与人脑髓母细胞瘤发病的关系。方法：应用ＳＰ免疫组化技术检测４５例术中切除的肿瘤标本的石蜡切片。结果：Ｐ１６蛋白在４５例髓母细胞瘤中的表达缺失率为８０％。而在１０例正常脑组织中的表达率为１００％。结论：Ｐ１６蛋白的缺失与髓母细胞瘤的发生有密切关系，其中的具体机制有待于在今后的研究中阐明。     

p53及mdm2在脑膜瘤中的表达及意义

脑膜瘤是中枢神经系统常见肿瘤之一,其发生机制仍然不清楚,随着肿瘤分子生物学研究的进展,目前认为脑膜瘤的发生和发展与癌基因活化及抑癌基因失活有关,mdm2瘤基因产物过表达可能使脑膜瘤中野生性p53失活,p53和mdm2在脑膜瘤的发生发展中可能发挥协同作用。     

MicroRNAs在胶质母细胞瘤中的应用进展

MicroRNAs（miRNAs）是近年来发现的一类普遍存在于动物和植物体内具有调控功能的非编码小分子RNA。多项研究发现miRNA可以抑制胶质母细胞瘤细胞系的增殖、诱导肿瘤细胞凋亡、抑制肿瘤细胞的迁移性、下调多种靶基因的表达。检测miRNAs在胶质母细胞瘤中的表达水平变化对肿瘤的诊断、预后及治疗提供了新的方向,本文对miRNAs在胶质母细胞瘤中的应用现状作一详细阐述。     

IDH1-R132H突变体通过miR-191-5p/p53轴调控U87MG胶质母细胞瘤干细胞增殖及凋亡

目的 探索IDH1-R132H突变抑制U87 MG胶质母细胞瘤干细胞增殖及诱导其凋亡的可能机制。方法 (1)以U87 MG细胞为研究对象,采用慢病毒转染构建IDH 1-R132H突变型及野生型细胞株,并诱导为胶质母细胞瘤干细胞,观察细胞球形成情况;流式细胞术检测肿瘤干细胞标志物CD133表达水平;CCK-8法检测细胞增殖情况和PI/Annexin V-FITC双染法检测细胞凋亡情况;qRCP和Western blot法分别检测IDH1、miR-191-5p及p53表达水平。(2)以NOD/SCID荷瘤小鼠作为研究对象,在体内水平考察miR-191-5p、p53表达及肿瘤生长情况。结果IDH1-R132H突变能够在体内外抑制U87 MG胶质母细胞瘤干细胞增殖(P<0.01)及分化(P<0.05),诱导其凋亡(P<0.01),下调miR-191-5p表达(体内P<0.05,体外P<0.001),上调p53(P<0.001)及其编码基因TP53(体内P<0.01,体外P<0.000 1)表达。结论 IDH1-R132H突变引起的U87 MG胶质...     

视网膜母细胞瘤中MDM2、P16和P53的表达及其意义

目的 研究P16、P53和癌基因MDM2在视网膜母细胞瘤的表达作用。方法 对已明确诊断的42例视网膜母细胞瘤标本采用免疫组织化学方法检测P16、P53和MDM2表达。结果 42例标本中P16、P53和MDM2阳性检出率分别是35．7％、69．1％和38．1％，P53和MDM2的共表达率为23．8％。结论 P16、P53和MDM2在视网膜母细胞瘤的产生和发展过程中起重要作用。     

Mdm2和p53基因在颅内非生殖细胞瘤性生殖细胞肿瘤中的表达意义

目的 研究鼠双微基因2(mdm2)基因和p53基因在颅内非生殖细胞瘤性生殖细胞肿瘤患者(NGGCTs)中的表达及意义. 方法 利用半定量RT-PCR技术检测了15例NGGCTs肿瘤(成熟畸胎瘤6例,未成熟畸胎瘤5例,卵黄囊瘤2例,绒毛膜上皮癌2例)中mdm2和p53 mRNA的表达,并与正常人群进行比较,另外检测p53基因5～8外显子的突变情况.结果 p53和mdm2mRNA在各类NGGCTs中均有较高水平表达,与正常对照组比较差异有统计学意义(P=0.000);p53mRNA在各类肿瘤中表达强度差异无统计学意义(P=0.056);mdm2基因在非生殖细胞瘤性恶性生殖细胞肿瘤(NGMGCTs)中表达强度较成熟畸胎瘤高,差异有统计学意义(P=0.000);mdm2和p53mRNA的表达强度无显著相关性(r=0.418,P=0.121);15例NGGCTs肿瘤均未检测到p53基因的突变.结论 mdm2基因异常表达与NGMGCTs肿瘤关系密切,p53基因突变并非NGGCTs形成的主要原因,mdm2和p53之间相互作用共同影响NGGCTs肿瘤的发生发展过程.     

Alterations of cell cycle regulatory genes in primary (de novo) and secondary glioblastomas

Primary glioblastomas develop rapidly de novo through a genetic pathway characterized by amplification/overexpression of EGFR and of MDM2 genes. Secondary glioblastomas develop more slowly through progression from low grade or anaplastic astrocytoma and show a high incidence of a p53 mutation. In the present study, primary and secondary glioblastomas were analyzed for p16 deletions and CDK4 amplification by differential PCR and for loss of expression of the retinoblastoma (RB) gene by immunohistochemistry. Except for one case, alterations in the structure or expression of p16, CDK4 and RB were mutually exclusive. The overall incidence of aberrant expression of these genes coding for components of the cell-cycling-regulatory system was similar in primary (14/28; 50%) and secondary glioblastomas (9/23; 39%). However, p16 deletions were significantly more frequent in the former (10/28; 36%) than in the latter (1/23, 4%; P = 0.0075), suggesting that this alteration constitutes an additional genetic hallmark of the primary (de novo) glioblastoma. Received: 2 June 1997 / Revised/Accepted: 10 July 1997     

RGS16与p53在人胶质瘤中的表达及相关性研究

目的 研究G蛋白信号调节子16(RGS16)与p53在人胶质瘤中表达及其相关性.方法 利用免疫组织化学链霉亲合素-生物素-过氧化物酶复合物(SABC)法检测42例胶质瘤标本中RGS16与p53的表达.结果 RGS16在10例胶质瘤旁正常脑组织有8例神经元阳性但胶质细胞阴性、42例胶质瘤中37例肿瘤细胞阳性,二者差异显著(P<0.05);p53在瘤旁正常脑组织中阴性,胶质瘤中15例阳性,差异明显(P<0.05);RGS16、p53表达均与病理分型、分级无关(P>0.05);其中,RGS16与p53共同阳性表达11例,共同阴性表达1例,Kappa检验二者表达呈负相一致(P<0.05).结论 RGS16在胶质瘤中高表达而与病理分级无关,推测RGS16可能在胶质瘤发生中起作用.另外,胶质瘤中RGS16与p53表达呈负相关.     

Epidermal growth factor receptor and p53 protein expression in human glioblastomas

p53 mutations and amplification of epidermal growth factor receptor (EGFR) gene are the most frequently detected genetic alterations in glioblastomas; thus, these changes seem to delineate two subgroups of glioblastomas: those originated de novo and those originated from preexistent low grade astrocytomas. Paraffin-embedded surgical specimens of 30 human glioblastomas were analyzed immunohistochemically for the presence of p53 protein and EGFR. Approximately half of the cases were p53 protein-positive while one-third were EGFR positive. Only three cases were positive for both p53 protein and EGFR. There was no difference between the average ages of patients with only-p53-positive, and double-negative tumors, while three glioblastomas with both p53 protein and EGFR immunopositivity occured in older patients (mean age 67.0 years, p < 0.02). Patients with only-EGFR-positive tumors were younger, but not significantly (44.3 years, p < 0.1). This study supports the notion that there are two main subpopulations of glioblastoma—with EGFR and with p53 protein overexpression.     

胶质瘤细胞周期蛋白、p53表达和DNA含量分析

本研究在手术中应用激光扫描细胞计数仪(laser scanning cytometry,LSC)分析胶质瘤细胞的DNA含量和细胞周期,并结合术中病理诊断,来判断肿瘤恶性程度和决定切除范围,术后对同一标本用免疫组化分析细胞周期蛋白(Cyclin)B1、D1和p53的表达.     

Neuroimaging Characteristics in Subgroup of GBMs with p53 Overexpression

Glioblastoma multiforme (GBM) is a heterogeneous group of tumors, and neuroimaging characteristics have not been well-defined in molecular subgroups. Eighty-five patients with GBM were analyzed regarding imaging characteristics and correlation to p53 expression. The p53 positivity was graded according to percentage of positive cells (Grade 0, for < 10%; Grade 1, for <25%; Grade 2, for 26-50%; Grade 3, for >50% labeled cells). Imaging characteristics evaluated in the preoperative MRI were location and number of lesions, dimensions of enhancing lesion and of surrounding edema, mass effect, tumor borders, enhancement pattern after intravenous contrast administration, and tumor necrosis. Eighteen tumors had p53 expression >50% in immunohistochemical staining. Preoperative MRI of patients harboring those tumors with high p53 positivity revealed typical lesions with ring enhancement pattern and well-defined borders in T1-weighted images with contrast, and they were significantly different from other groups of p53 expression. There was no difference in terms of location and number of the lesions, dimensions of enhancing lesion and surrounding edema, mass effect, and the tumor necrosis between four different groups of p53 expression. A special subgroup of GBMs with p53 overexpression has ring enhancement pattern and well-defined border on MRI that may be influential in preoperative planning and postoperative management of adjunct therapy.     

小儿脑胶质瘤p16基因的表达

目的：检测２０例小儿脑软质瘤中Ｐ１６基因及其蛋白的存在情况。方法用聚合酶链式反应－单链构象多态性分析和免疫组织化学技术检测了２０例１－１４岁小儿脑胶质瘤。成果显示Ｐ１６基因和Ｐ１６蛋白的丢失率分别为５０％（１０／２０％）及（５／２０）。结论本结果提示Ｐ１６基因和蛋白缺失可能与部分小儿脑有质瘤发生,发展有关。     

Chromosome 1p and 19q status and p53 and p16 expression patterns as prognostic indicators of oligodendroglial tumors: A clinicopathological study using fluorescence in situ hybridization

To verify the prognostic implications of the statuses of chromosome 1p and 19q and the expressions of p53, p16 and GFAP in oligodendrogliomas, we investigated these parameters and correlated the results with patient outcome. Twenty-seven cases of low-grade oligodendroglioma (LO) and 29 cases of anaplastic oligodendroglioma (AO) were analyzed by FISH for 1p and 19q status and by immunohistochemistry for p53, p16, and GFAP expression using a tissue microarray. Direct sequencing of the p53 gene was also performed. 1p deletion was observed in 39 of 56 patients (69.9%), and 19q deletion in 41 of 56 (73.2%). Combined loss of 1p and 19q was found in 38 of 56 (67.9%) and exhibited distinct concomitant deletion (P = 0.000). p53 overexpression was observed in 17 cases (30.3%), GFAP expression in 18 cases (32.1%), and p16 loss in 40 cases (74%) of oligodendrogliomas. The expressions of p53 and GFAP were more frequent in AO than in LO (P = 0.015 and 0.001). In contrast, p53 expression was more common in oligodendrogliomas with an intact 19q (P = 0.029), or an intact 1p (P = 0.071). Only five of 14 patients with p53 expression showed TP53 mutation, which was inversely correlated with 1p deletion (P = 0.036). Patients with combined loss of 1p and 19q exhibited better overall survival (P = 0.045). Patients with p53 expression without combined 1p and 19q loss showed poor overall survival (P < 0.000). However, TP53 mutation along with 1p and 19q status could not predict patient outcome. Patients with p16 loss without combined 1p and 9q loss showed poor overall survival (P = 0.011). Therefore, in oligodendrogliomas, the absence of the combined deletion of 1p and 19q and the aberrant expression of p53 or loss of p16 could be used as poor prognostic markers.     

Overexpression of p53 but not Rb in the cytoplasm of neurons and small vessels in an autopsy of a patient with Cockayne syndrome

Cockayne syndrome presents senescence‐like changes starting in early infancy; however, the mechanism of premature aging remains unclear. In an autopsy of a 23‐year‐old woman with Cockayne syndrome, we evaluated the correlation between Cockayne pathology and the expression patterns of the senescence‐associated proteins p53 and Rb. Neuropathological findings in this case revealed basal ganglia calcification, tigroid leukodystrophy, bizarre reactive astrocytes, severe cerebellar atrophy with loss of Purkinje cells, and arteriolar/neuronal calcifications in the hypothalamus. Multiple arteriolar calcifications and sclerotic changes were seen in the central nervous system and kidney, but the endothelium of the aorta and coronary arteries remained intact appropriately for the individual's age without any finding of arteriosclerosis. Overexpression of p53 protein was confirmed in the cytoplasm of neurons in the basal ganglia, thalamus, hypothalamus, hippocampus and cerebellum, of arteriolar endothelial cells of the cerebrum and renal glomerular capillaries, and of cutaneous epithelial cells. The distribution of p53 overexpression was coincident with that of pathological alteration, such as neuronal loss, calcification and atrophy. High expression of p53 was localized in the cytoplasm, not in the nucleus. In contrast to p53, Rb was not expressed in any senescence lesion. In terms of senescence, distinct differences are found among organs in a patient with Cockayne syndrome. This segmental progeria differs from natural aging, and implicates p53 overexpression in the etiology of CS.     

抑癌基因p16蛋白在脑胶质瘤中的缺失及意义

目的 研究ｐ１６蛋白的缺失率与脑胶质瘤性程度的关系。方法 应用ＳＰ免疫级化检测７２例人脑胶质瘤,４个人脑体外恶性胶质瘤细胞系及１０例正常脑组织中抑癌基因ｐ１６蛋白的表达,结果 正常脑组织、Ｉ级、ＩＩ级、ＩＩＩ级、ＩＶ级、ＣＬ中ｐ１６蛋白的缺失率分别为０．１０％,３１．８％,６３．２％,７１．４％,１００％,脑胶质瘤细胞系,高恶度脑胶质瘤（ＷＨＯ,ＩＩＩ级～ＩＶ级）与低恶度脑胶质瘤（ＷＨＯ,Ｉ级～Ｉ级）之间差异显（Ｐ〈０．０５）,结论 ｐ１６蛋白的缺失率与脑胶质瘤的汪事分极和恶性程度密切相关,提示ｐ１６基因在脑胶质瘤的发生,发展过程中起重要作用。