星形细胞肿瘤中MDM2蛋白与突变型p53蛋白的表达及其？…

目的：探讨ｍｄｍ－２基因表达和ｐ５３基因突变在星形细胞肿瘤发生发展中的作用及两者的相关性。方法：采用ＳＡＢＣ免疫组化法对１２０例星形细胞肿瘤进行检测。结果：在分化不良性星形细胞瘤及多形性胶质母细胞瘤中，ＭＤＭ２蛋白的阳性率分别为３０．００％和３５．２９％，突变型ｐ５３蛋白的阳性率分别为３５．００％和４４．１２％，均明于高于高分化星形细胞瘤（４．３５％和６．５２％）；突变型ｐ５３蛋白染色阴性的星形细     

星形细胞瘤中PTEN、Mdm2和p53的表达及其相关性研究

目的: 探讨不同组织病理分级的星形细胞瘤中PTEN、Mdm2和p53的表达水平, 并分析PTEN影响Mdm2、p53表达的信号转导机制。方法: 采用免疫组织化学方法检测68例星形细胞瘤标本中PTEN、Mdm2和p53的表达水平。结果:星形细胞瘤中PTEN、Mdm2、p53的表达水平分别是54.4%(37/68)、41.2%(28/68)、45.6%(31/68)。PTEN阳性标本中Mdm2的表达率(24.3%, 9/37)与PTEN阴性标本中该蛋白的表达率(61.3%, 19/31)相比差异显著, 统计学分析显示PTEN表达与Mdm2表达呈负相关(P＜0.01)。Mdm2表达和p53表达一致符合率达66.2%(45/68), 两者的表达密切相关(P＜0.05)。结论: (1)PTEN、Mdm2和p53表达与星形细胞瘤的组织病理分级相关。(2)抑癌基因PTEN可以下调癌基因Mdm2的表达水平。(3)Mdm2和p53的表达存在一致性。     

p53基因突变及其蛋白表达与脑胶质瘤

ｐ５３基因突变是人类肿瘤中最常见的突发之一，胶质瘤约有１／３发生ｐ５３基因突变。通过对胶质瘤ｐ５３基因突变和蛋白表达的研究，提出了多形性胶质母细胞瘤的三种不同起源方式，发现ｐ５３蛋白表达在脑胶质瘤与反应性胶质增生的鉴别诊断中有一定的作用，但多数资料的研究结果提示ｐ５３蛋白表达对脑胶质瘤患者的预后判断无意义。     

星形细胞瘤中cyclinD1、p16表达及相互关系

目的　探讨cyclinD1和 p16在星形细胞瘤恶性转变中表达的变化及其相互关系。 方法　采用免疫组化S P法、原位分子杂交和图像分析检测 13例正常大脑组织和 5 8例星形细胞瘤 (Ⅰ～Ⅳ )cyclinD1和 p16的表达。 结果　cyclinD1mRNA的表达在星形细胞瘤组织与正常脑组织中的差异有显著性 (P <0 0 5 ) ,随着肿瘤恶性程度增高 ,表达阳性率增高。p16蛋白和p16mRNA的表达随肿瘤恶性程度增加逐渐降低 ,差异有显著性 (P <0 0 5 )。但肿瘤组织中 p16蛋白和p16mRNA两者表达量都高于正常脑组织。结论　癌基因cyclinD1过度表达和抑癌基因 p16表达降低都参与星形细胞瘤恶性进程 ,且发生恶性转变时 ,高表达的cyclinD1刺激了p16的表达。cyclinD1和 p16表达的变化与星形细胞瘤发生发展有关     

抑癌基因p53及蛋白产物在星形细胞瘤中的表达

抑癌基因ｐ５３及蛋白产物在星形细胞瘤中的表达郭琳琅曹长安肖莎区士欢采用核酸分子原位杂交技术和免疫组化方法观察了ｐ５３基因在３７例星形细胞瘤中的表达情况，探讨ｐ５３基因与星形细胞瘤发生的关系。１材料和方法１．１材料选自我院神经外科手术切除星形细胞瘤标本...     

星形细胞肿瘤中PTEN蛋白表达及与微血管密度的相关性

目的 :研究不同恶性程度星形细胞肿瘤中PTEN蛋白的表达及与肿瘤微血管密度 (MVD)之间的相关性。方法 :应用免疫组织化学S P法检测 72例星形细胞肿瘤和非肿瘤脑组织中PTEN蛋白的表达并对肿瘤MVD计数 ,分析其意义及两者间的相关性。结果 :PTEN阳性染色主要定位于细胞质中 ,肿瘤总阳性率为 5 4 17% (39/ 72 ) ,其中Ⅱ、Ⅲ、Ⅳ级者PTEN阳性表达率分别为 81 82 % (18/ 2 2 )、42 86 % (15 / 35 )和 37 5 0 % (6 / 15 )。星形细胞瘤PTEN表达率明显高于间变性星形细胞瘤和多形性胶质母细胞瘤 (P <0 0 1) ;星形细胞肿瘤MVD计数 ,72例肿瘤平均MVD为 38 2 2 ,其中Ⅱ、Ⅲ、Ⅳ级者MVD分别为2 8 81± 9 42、41 17± 13 96和 5 3 11± 15 85 ,肿瘤组各级别间差异均有显著性 (P <0 0 1) ;星形细胞瘤以窦状扩张型血管、间变性星形细胞瘤以芽状或条索状血管为主 ,而多形性胶质母细胞瘤部分以球状血管丛为特征 ;PTEN蛋白的表达与肿瘤中MVD呈负相关 (r =- 0 5 11,P <0 0 1)。结论 :PTEN基因突变或缺失在星形细胞肿瘤的发生发展中可能起重要作用 ,与肿瘤恶性分化程度密切相关 ;PTEN表达的检测结合MVD与形态的测定有助于提高评估患者术后生存的准确性     

肺鳞状细胞癌中p53蛋白表达及p53基因突变的检测

目的 通过检测肺鳞状细胞癌及癌旁组织中Ｐ５３蛋白积聚及相同癌组织中Ｐ５３基因的突变，探讨Ｐ５３蛋白积聚及Ｐ５３基因突变在肺鳞癌发病中的意义。方法 采用免疫组化和银染－ＰＣＲ－ＳＳＣＰ方法检测１２０例肺鳞癌及癌旁肺组织中Ｐ５３蛋白的状况及相同鳞癌组织中，Ｐ５３基因５、６、７、８外，显子突变的情况。结果 Ｐ５３蛋白了性率为５２．５％，Ｐ５３基因突变率为５６．７％，突变便数在第５、６、７、８外显子的分布     

食管鳞状细胞癌p53基因突变及其蛋白表达

食管鳞癌常伴有ｐ５３基因突变和（或）ｐ５３蛋白积聚。文献报道ｐ５３基因改变与ｐ５３蛋白积聚常出现不一致的现象〔１，２〕。我们应用ＰＣＲＳＳＣＰ及免疫组化方法探讨食管鳞癌ｐ５３基因突变与ｐ５３蛋白表达的关系。１　材料和方法１１　材料　取食管癌新鲜组织３０例，同一标本分为２份，１份按常规方法提取ＤＮＡ，另１份经福尔马林固定，石蜡包埋，连续切片。１２　ＰＣＲＳＳＣＰ〔３〕　ＰＣＲ常规扩增反应后，取１０μｌＰＣＲ产物与等量电泳缓冲液混合，９６℃变性５ｍｉｎ后立即置冰浴，电泳后，凝胶经固定、银染、…     

星形细胞肿瘤p53蛋白和PCNA免疫组化及其临床病理意义

应用免疫组化和图象分析技术对人脑星形细胞肿瘤中抑癌基因ｐ５３蛋白（４７例）和增殖细胞核抗原（ＰＣＮＡ）（９７例）的定位、分布及反应强度与分级和预后的关系进行了研究。结果显示；３种ｐ５３蛋白抗体的阳性率为２３．４％～６６．７％，其中ＣＭ－１抗体阳性率高于ｐＡｂ１８０１和ｐＡｂ２４０；ｐ５３表达水平在Ⅱ～Ⅳ级高于１级，并与ＰＣＮＡ标记指数之间相关。ＰＣＮＡ反应强度既与分级相关，又与预后相关，对于分析星形细胞瘤增殖活性和恶性程度有重要意义。     

AgNORs,p53癌基因蛋白在胶质细胞增生和胶质瘤中的表达

目的：探讨核仁组成区嗜银蛋白（ＡｇＮＯＲｓ），ｐ５３蛋白在胶质细胞增生和胶质瘤中的表达。方法：运用免疫组化和形态半定量技术，对胶质细胞增生和星形细胞瘤分别标记ＡｇＮＯＲｓ（３７例），ｐ５３蛋白（３３例）的表达。结果：ＡｇＮＯＲｓ，ｐ５３蛋白在胶质细胞增生和Ⅰ级星形细胞瘤以及Ⅱ、Ⅲ、Ⅳ级星形细胞瘤中的表达存在差异性，各组间统计学处理Ｐ＜０．０１，差异有显著性。结论：ＡｇＮＯＲｓ、ｐ５３蛋白可作为鉴别胶质细胞增生和Ⅰ级星形细胞瘤有用的参考指标，两者表达随着星形细胞瘤级别增加而增强，具有正相关性，能较好地反映星形细胞瘤的恶性程度     

鼻咽癌中hTERT和p53的表达及其相关性

目的　研究人端粒酶逆转录酶 (hTERT)和 p5 3在鼻咽癌中的表达及其对预后的影响 ,并分析hTERT与抑癌基因p5 3的相关性。 方法　用免疫组化S P法分别检测hTERT及 p5 3在 84例鼻咽癌组织、8例癌旁黏膜上皮非典型增生组织和16例鼻咽黏膜慢性炎组织中的表达。结果　 (1)hTERT在鼻咽癌组织 癌旁黏膜上皮非典型增生组织和鼻咽黏膜慢性炎组织中的阳性表达率分别为 83 4 % (70 / 84 )、0 (0 / 8)和 0 (0 / 16 ) ;p5 3在上述 3种组织中的阳性表达率分别为 5 6 % (4 7/ 84 )、5 0 %(4 / 8)和 0 (0 / 16 ) ;两种基因表达在癌与非癌组间差异均有显著性 (P <0 0 0 1)。 (2 )hTERT阳性表达患者的平均生存期、5年生存率和中位生存期均低于hTERT阴性者 ,且差异有显著性 (P <0 0 5 )。p5 3阳性和阴性表达患者的预后组间差异无显著性 (P >0 0 5 )。 (3)鼻咽癌组织中hTERT与 p5 3的表达一致率为 6 3% (5 3/ 84 ) ,存在显著相关性 (P <0 0 5 )。 结论　hTERT可作为临床诊断鼻咽癌的一个潜在指标 ,且对临床判断预后有重要意义。p5 3的表达对鼻咽癌的临床诊断具有一定价值 ,但其特异性不强 ,对判断预后也无显著意义 ;p5 3很可能参与了对hTERT表达的调控 ,但可能以不同方式出现     

An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms

Immunohistochemical detection of intranuclear p53 gene product may indicate mutation of the p53 suppressor gene on chromosome 17p. We used six commercially available antibodies for p53 immunohistochemistry on 19 archival colorectal neoplasms and compared the results with the mutation status of the p53 gene and 17p allelic deletion status. By Friedman's ranking analysis, use of mouse monoclonal antibody DO7 with Target Unmasking Fluid (TUF) for antigen retrieval was the most sensitive and specific procedure (P<0·0001). Six of 7 cases with high expression (p53 Labeling Index >30 per cent using a CAS 200 image analyser) had p53 mutation. Of seven tumours without expression (LI < 1 per cent), six had no mutation and one had a truncating mutation which prohibited nuclear localization of gene product. The low expression group (1 per cent < LI <30 per cent, n = 5) consisted of three tumours without and two tumours with mutation. The sensitivity of high expression with the DO7–TUF method for p53 gene mutation was 67 per cent with specificity of 90 per cent, predictive value of a positive of 86 per cent, predictive value of a negative of 75 per cent, and efficiency of 79 per cent. This study suggests that immunohistochemistry is valuable for assessing p53 gene mutations in colorectal neoplasms, but further study is needed to elucidate the precise link between immunohistochemistry and molecular genetic alterations.     

胃腺癌中p53、E-cadherin的表达及其预后因素分析

目的 研究胃腺癌组织中p53、E-cadherin的表达,分析它们和临床病理参数对预后的影响.方法 采用组织芯片和免疫组化检测150例胃腺癌中p53、E-cadherin的表达,分析它们和临床病理参数对预后的影响.单因素分析用Kaplan-Meier法计算累积生存率并比较患者术后平均生存时间,多因素分析用COX回归.结果 150例胃腺癌中p53阳性率为31.3%;E-cadherin阳性率为91.3%.随访到的74例胃腺癌患者1年生存率为83.8%,3年生存率为70.3%,5年生存率为63.5%.单因素分析年龄、分化程度、Laurén分类、浸润深度、淋巴结状况、pTNM分期是影响胃腺癌预后的因素;多因素分析p53、年龄、淋巴结状况为影响胃腺癌预后的独立因素(P<0.05).结论 p53、年龄、分化程度、Laurén分类、浸润深度、淋巴结状况和pTNM分期是影响胃腺癌预后的因素,而E-cadherin和组织学分类不是影响胃腺癌预后的因素.     

Overexpression of p53 protein and MDM2 in papillary carcinomas of the thyroid: Correlations with clinicopathologic features

Expression of p53 protein and MDM2 was evaluated in paraffin-embedded tissue from 78 patients with papillary carcinomas of the thyroid (PCT), in order to elucidate the relationship between them and their correlations with some clinicopathologic features implicated in tumor progression. These proteins were expressed in nuclei of tumor cells, but not in non-tumor cells. Staining was defined as positive when 10% or more of tumor cells expressed these proteins. The number of cases positive for p53 protein was 21/78 (27%), and that positive for MDM2 was 26/78 (33%). Co-overexpression of p53 protein and MDM2 was observed in 12/78 cases (15%). A significant positive relationship was found between them (P < 0.01); p53-positive cases tended to be also positive for MDM2 and vice versa. Statistical analysis revealed that overexpression of p53 protein significantly correlated with large tumor size (P = 0.0271) and the presence of capsular invasion (P = 0.04). There were significant positive correlations between tumor size and intrathyroidal invasion and between tumor size and capsular invasion in PCT, suggesting that p53 protein overexpression is associated only with tumor progression (tumor size). However, we could not find any significant correlations between MDM2 expression and clinicopathologic features. Our findings suggest that overexpression of p53 protein and MDM2 in papillary carcinoma of the thyroid is associated with the progression of the tumors, and that p53 may be a marker of the progression of PCT.     

骨肿瘤MDM2和p53基因的改变

目的从基因水平研究ＭＤＭ２和ｐ５３基因在骨肿瘤中的表达，探讨其在骨肿瘤发生发展中的作用。方法用地高辛标记原位杂交技术研究了３８例骨肿瘤（骨肉瘤１２例，软骨肉瘤１０例，骨巨细胞瘤１４例，软骨母细胞瘤２例）ＭＤＭ２和ｐ５３的表达情况，并分析两种基因表达之间的相互关系。结果ＭＤＭ２在骨肉瘤、软骨肉瘤和骨巨细胞瘤中的阳性率分别为４１．７％、５０．０％和３５．７％。ｐ５３的阳性率分别为５８．３％、４０．０％和２１．４％。２例软骨母细胞瘤ＭＤＭ２和ｐ５３均为阳性。ＭＤＭ２与ｐ５３基因表达呈显著正相关（Ｐ＜０．００５）。结论ＭＤＭ２和ｐ５３基因改变是骨肿瘤的一种常见现象，可能参与骨肿瘤的发生与发展。     

大肠腺癌p53基因cDNA突变与突变型p53基因蛋白表达的相互关系和意义

目的：探讨大肠腺癌突变型ｐ５３基因蛋白表达与ｐ５３基因ｃＤＮＡ突变间的相互关系和意义。方法：对１００例新鲜大肠腺癌组织采用ＰＡｂ２４０单克隆抗体免疫组织化学染色（ＬＳＡＢ法）检测突变型ｐ５３基因蛋白表达、ＲＴ－ＰＣＲ－ＳＳＣＰ检测ｐ５３基因ｃＤＮＡ突变，并比较它们间相互关系。结果：１００例大肠腺癌中，７６例ＰＡｂ２４０单抗阳性（７６％），５１例ｐ５３基因ｃＤＮＡ突变阳性（５１％）；ＰＡｂ２４０单抗反应与ｐ５３基因ｃＤＮＡ突变比较，两者皆阳性４９％，两者中一者阳性２９％，两者皆阴性２２％（Ｐ＜０．０００１）。结论：ｐ５３基因ｃＤＮＡ突变与其基因蛋白产物结构改变高度吻合，大肠腺癌ｐ５３基因ｍＲＮＡ（ｃＤＮＡ）突变是参与和影响突变型ｐ５３基因蛋白结构改变和生物学行为的主要因素     

Expression of cyclooxygenase-2 and its relationship to p53 accumulation in colorectal cancers

PURPOSE: Cyclooxygenase (COX)-2 is an inducible isoform responsive to cytokines, mitogens, and growth factors, and is believed to be an important enzyme related to colorectal cancer (CRC). Existing evidence suggests that COX-2 expression is normally suppressed by wild-type p53 but not mutant p53, suggesting that loss of p53 function may result in the induction of COX-2 expression. The aim of this study was to determine the relationship between COX-2 expression and p53 levels in CRC. MATERIALS AND METHODS: Patients with sporadic colorectal adenocarcinoma (n=161) who underwent curative surgery in Chosun University Hospital were enrolled in this study. Expression of COX-2 and p53 proteins was examined by immunohistochemistry in paraffin-embedded cancer tissue blocks, and the relationship between COX-2 and/or p53 expression with clinicopathologic parameters was analyzed. RESULTS: Expression of COX- 2 was positive in 47.8% of colorectal cancers, and significantly associated with the depth of tumor invasion (p= 0.042). In contrast, p53 was positive in 50.3% of the cases, and was associated with both age (p=0.025) and the depth of tumor invasion (p=0.014). There was no correlation between COX-2 expression and p53 expression (p=0.118). CONCLUSION: These results suggest that COX-2 expression might play an important role in the progression of colorectal cancer. However, COX-2 expression was not associated with mutational p53. Further studies are needed to clarify the regulatory mechanisms governing COX-2 overexpression in colorectal cancers.     

Expression of p53 protein in infiltrating and in-situ breast carcinomas.

Five antibodies directed against the whole or part of p53 protein have been used to detect the protein immunohistochemically in 70 infiltrating breast carcinomas and 10 ductal carcinomas in situ. Mutations are known to occur in different conserved domains, and the antibodies employed spanned the expected sites. p53 protein was identified in 53 per cent of infiltrating carcinomas using the antibodies PAb 240, PAb 1801, C19, and JG8. The antibody PAb 421 detected the protein in 31.5 per cent; all positive with the other antibodies. Well-differentiated oestrogen receptor-positive tumours had a low incidence of p53 detection. Variation in the percentage of reactivity was seen between carcinomas and in some cases between different antibodies in the same cancer. Those carcinomas with a high percentage of positive cells with all antibodies were more likely to have metastasized to nodes, be at an advanced stage, and be oestrogen receptor-negative/epidermal growth factor receptor-positive. There was no significant correlation with c-erbB-2 protein expression or retinoblastoma protein loss. p53 protein was detected in a high proportion of cells in three of the six comedo ductal carcinomas in situ studied but either not at all or at a lower level in tumours of the cribriform type. p53 mutations are common in breast carcinomas, but heterogeneity within individual tumours is frequent. Marked expression of p53 appears to relate to tumour progression.     

Expression of the p53 protein in a spectrum of astrocytic tumours.

Many human cancers are characterized by mutations of p53, a nuclear phosphoprotein which controls elements of the cell cycle. Turnover of p53 in normal cells is rapid, and the minute quantities of protein that are usually present are not detected by immunocytochemical methods. Mutations of the p53 gene in tumour cells are associated with a slower turnover and subsequent accumulation of the protein in both nucleus and cytoplasm. Genetic abnormalities of the short arm of chromosome 17, which is the site of the p53 gene locus, are a feature of astrocytic tumours. Using a panel of five antibodies to p53 and a standard immunocytochemical method, we found detectable quantities of p53 in the cells of 3/16 diffuse astrocytomas, 8/14 anaplastic astrocytomas, and 24/34 glioblastoma multiforme. Progression of one patient's tumour from a diffuse to an anaplastic astrocytoma was characterized by the accumulation of p53. The more malignant histological features of anaplastic astrocytoma and glioblastoma multiforme appear to be reflected by a greater incidence of p53 accumulation.