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1.
免疫组化和PCR—SSCP检测p53基因异常的一致性探讨 总被引:1,自引:0,他引:1
目的:探讨免疫组化检测p53蛋白表达和PCR-SSCP检测p53基因突变的一致性。方法:单克隆抗体DO-7检测85例非小细胞肺癌(NSCLC)的p53蛋白表达,PCR-SSCP检测其中31例腺癌的p53基因突变。结果:85例NSCLC中p53蛋白表达阳性率为68%(58/85),31例腺癌中p53蛋白表达阳性率为61%(19/31),14例(46%)出现p53基因5~8外显子突变,p53蛋白免疫组化和PCR-SSCP检测p53基因突变无显著相关(χ2=0.1,P=0.76),其一致率为52%。结论:p53蛋白表达并不能很好地反映p53基因突变。 相似文献
2.
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 相似文献
3.
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%,均明显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胞肿瘤中,MDM2蛋白阳性率(26.15%)明显高于其染色阳性的肿瘤(9.38%)。结论:MDM2蛋白及突变型p53蛋白在星形细胞肿瘤中的表达均与该肿瘤的分化程度有关;mdm-2基因扩增及产物MDM2蛋白过度表达,可能是突变型p53蛋白染色阴性的星形细胞肿瘤发生的分子基础 相似文献
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bcl-2、p53蛋白及PCNA表达与横纹肌肉瘤临床病理相关性研究 总被引:3,自引:0,他引:3
目的:研究横纹肌肉瘤(RMS)中bcl-2、p53、PCNA表达与其临床病理的相关性。方法:对50例(随访41例)横纹肌肉瘤进行免疫组化ABC法标记。结果:bcl-2、p53基因蛋白和PCNA,发现bcl-2、p53、PCNA阳性表达率分别为28%、72%、70%,其阳性表达与年龄、性别及不同组织类型的RMS无关(P>0.05)。但与分化程度有关,p53、PCNA在低分化RMS阳性率分别为85%、95%,显著高于高分化RMS42.8%和14.3%(P<0.05),随访存活1年以内的p53、PCNA阳性率均为86.7%,亦明显高于存活超过3年以上的阳性率33.3%和41.7%(P<0.05)。而bcl-2在低分化RMS阳性20%显著低于高分化71.4%(P<0.05),随访存活1年以内的阳性率13.4%明显低于存活超过3年以上的41.4%(P<0.05)。p53与bcl-2阳性表达呈明显负相关,p53阳性率越高,而bcl-2阳性率越低。结论:PCNA、p53、bcl-2蛋白表达能比较准确地反映RMS的生物学特性,p53、bcl-2可作为肿瘤预后显著相关的有效指标。 相似文献
6.
骨肉瘤N—ras,c—myc基因异常及其蛋白产物的表达 总被引:1,自引:0,他引:1
目的:探讨癌基因N-ras,c-myc及其蛋白表达与骨肉瘤的关系,方法:Southernblot和免疫组织化学(LSAB法)同步检查9例人骨肉瘤N-ras,c-myc癌基因和其p21rasc-myc蛋白产物表达,结果:N-ras基因1例有为失改变,检出率11%(1/9),c-myc基因有3例为扩增改变,检出率33%(3/9),p21ras,c-myc基因蛋白表达阳性率分别为78%(7例),89%( 相似文献
7.
c─erbB─2、ras p21及p53在大肠癌表达的免疫组化研究 总被引:2,自引:0,他引:2
孟刚 《临床与实验病理学杂志》1995,(3)
对48例大肠癌连续切片进行c─erbB─2、rasp21及p533种癌相关基因产物的免疫组化ABC法及APAAP-IGSS双重标记研究,结果表明:(1)癌相关基因c─erbB─2、rasp21和p53阳性表达率在癌组织分别为50.2%(25/48)、43.8%(21/48)和54.2%(26/48);癌旁粘膜分别为25%(12/48)、18.8(9/48)和20.8%(10/48);而在"正常"结肠粘膜则分别为12.5%(6/48)、6.3%(3/48)和0.(2)有2种以上癌相关基因产物同时表达者在癌组织中有26例(54.2%).在癌旁粘膜有5例(10.5%),而在正常粘膜则未见有2种癌相关基因同时表达,(3)癌组织中c─erbB─2+p21、c─erbB─2+p53、p21+p53及c─erbB─2+p21+p53同时表达者分别为2.1%、12.5%、16.7%及22.9%,(4)APAAP-IGSS双重免疫标记结果表明,单一癌细胞可同时表达2种癌基因产物。上述结果提示:c─erbB─2、rasp21及p53可能与大肠病的发生有关,三者在大肠病的发生中可能起协同作用。 相似文献
8.
应用聚合酶链反应(PCR)方法检测31例SLE病人外周血单个核细胞(PBMC)Bcl-2/JH基因重排现象和流式细胞仪间接双标记法分析其T(CD3)、B(CD19)细胞Bcl-2蛋白的表达。结果显示,SLE病人T细胞Bcl-2蛋白表达明显高于正常人(42.95%±28.47%对比9.94%±4.96%,P=0.0004),尤其以活动期SLE病人为明显,而B细胞Bcl-2蛋白表达与正常人之间并无统计学差异(79.21%±10.69%对比81.96%±6.97%;P=0.4602)。7例SLE病人具有典型的Bcl-2/JH基因重排(占22.58%),且均为SLE活动期病人,其T细胞Bcl-2蛋白表达明显高于无基因重排的SLE病人,其B细胞Bcl-2表达并无差异(P>0.3905)。说明Bcl-2/JH基因重排现象可见于SLE,并与T细胞Bcl-2蛋白高表达有关,表明细胞凋亡抑制基因Bcl-2在SLE发病机制中具有重要作用。 相似文献
9.
p-MAPK、cyclinD1和p53蛋白在大肠癌中的表达及其相关性 总被引:3,自引:0,他引:3
目的:检测p-MAPK、cyclinD1和p53蛋白在大肠癌中的表达,并探讨其相关性。方法:免疫组织化学S-P法。结果:140例大肠癌中p-MAPK、cyclinD1和p53蛋白的阳性表达率分别为92.9%(130/140)、87.1%(122/140)和66.4%(93/140);50例相应癌旁肠粘膜中阳性表达率分别为4.0%(2/50)、6.0%(3/50)和2.0%(1/50)。三者阳性表达 相似文献
10.
肝癌组织中N—ras基因突变和p53蛋白表达 总被引:2,自引:1,他引:2
目的:研究N-ras和p53基因与肝癌发生,发展的关系。方法:应用多聚酶链反应-单链构象多态性分析法(PCR-SSCP)和免疫组化法,检测29例肝癌中的N-ras基因突变和p53蛋白的表达。结果,13例肝癌p53蛋白阳性(44.8%),表明广西地区肝癌中曾普遍存在p53基因的突变,肝癌及癌旁组织中N-ras基因在第2~37密码子间的突变率分别为79.31%和80.77%,22例有2个以上突变位点( 相似文献
11.
Molina P Pellín A Navarro S Boix J Carda C Llombart-Bosch A 《Virchows Archiv : an international journal of pathology》1999,435(6):596-605
TP53 and MDM2 genes and their protein expression were evaluated in frozen and paraffin-embedded tissue from 27 patients with malignant
fibrous histiocytoma to elucidate the relationship between them, their implication in tumor progression mechanisms and their
possible diagnostic-prognostic value in malignant fibrous histiocytoma. Single-strand conformation polymorphism analysis and
direct sequencing of polymerase chain reaction-amplified DNA were used to establish two TP53 mutations (7.4%): a point mutation and a 63-bp duplication. Amplification of the MDM2 gene was observed in two tumors (7.4%) by means of Southern-blot analysis, one of them also carrying the TP53 point mutation.
Immunohistochemical and Western-blot techniques were used to study nuclear accumulation of p53 and mdm2 proteins: 11 cases
(40.7%) with p53 protein expression and thirteen cases (48.1%) with mdm2 protein expression were detected. We confirmed overexpression
of mdm2 protein in eight of ten cases (80%) with p53 protein expression without TP53 gene mutation. Statistical analysis shows that simultaneous co-expression of p53 and mdm2 in malignant fibrous histiocytoma
is significantly correlated with survival in absence of gene alteration in contrast to the lack of statistical correlation
with survival of p53 protein expression alone.
Received: 13 April 1999 / Accepted: 14 July 1999 相似文献
12.
Pitfalls in the diagnosis of ectopic hamartomatous thymoma 总被引:3,自引:0,他引:3
We have investigated the immunohistochemical expression of p53, mdm2, p21/waf1 and bcl-2 proteins in 31 thymic epithelial tumours comprising five medullary thymomas (MDT), four mixed thymomas (MT), 12 cortical thymomas (CT), eight predominately cortical thymomas (PCT) and two well-differentiated thymic carcinomas (WDTC). We have found p53, mdm2, p21 and bcl-2 protein expression in 25/31, 8/31, 5/31 and 10/31 thymic epithelial tumours, respectively. Coexpression of p53 and mdm2 proteins was found in eight cases (three CT, four PCT and one WDTC). Five of them were also p21 positive and three p21 negative. Discordant p53+/mdm2−/p21− protein expression was found in 19 cases (three MDT, three MT, nine CT, three PCT and one WDTC). Mdm2 and p21 proteins were not expressed in the absence of p53 protein. Coexpression of bcl-2 and p53 proteins was found in seven cases (three MDT, three MT and one WDTC). Eighteen cases were p53+/bcl-2− (10 CT, seven PCT and one WDTC) and three cases (two MDT and one MT) were bcl-2+/p53−. Our findings indicate that in thymomas, p53 expression is more frequently associated with cortical histotypes while bcl-2 expression is strongly associated with medullary and mixed histotypes. In addition, there is an inverse correlation between p53 and bcl-2 protein expression in thymomas. Coexpression of p53/mdm2/p21 proteins may reflect thymomas with wild-type (wt), p53 gene since mdm2 and p21 proteins are inducible by wt p53 gene. However, in view of previous findings that p53 mutation is an early event in thymomas, the possibility of p53 gene mutation with p53-independent mdm2 and p21 expression should be considered in these cases. Discordant p53+/mdm2−/p21− protein expression may represent thymomas with p53 gene mutations unable to activate expression of mdm2 and p21 proteins. 相似文献
13.
Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival 总被引:1,自引:0,他引:1
The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers. 相似文献
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Kanavaros P Stefanaki K Rontogianni D Darivianaki K Vlychou M Papadaki E Eliopoulos G Bakiri M Matsouka C Kakolyris S Georgoulias V 《Clinical and experimental pathology》1999,47(5):231-238
The aim oof this study was to investigate the immunohistochemical expression of p53, mdm2, and waf1/p21 proteins in myelodysplastic syndromes (MDS), acute myelogenous leukaemias (AML), and chronic myeloproliferative disorders (CMPD). Paraffin-sections of bone marrow biopsies from 30 cases of MDS (6 cases of RAEB and RAEB-T) 22 AML (4 cases occurring in the setting of MDS), 16 chronic myeloproliferative disorders (CMPD), and 10 cases without alterations were investigated by immunohistochemistry for p53, waf1/p21, mdm2 and Ki67 proteins. P53 was detected in immature myeloid cells in 6/30 MDS (20%) and in 6/22 AML (27%) while it was not expressed in CMPD. Of the 6 p53 positive AML, 3 occurred as evolution of MDS and 3 were de novo acute leukaemias. Waf1/p21 was detected in 5/22 (23%) AML in immature myeloid cells. Waf1/p21 was also expressed in 18/30 (60%) MDS and 10/16 (63%) CMPD in variable proportion (5-25%) of the mature myeloid cells and megakaryocytes. Waf1/p21 was not detected in immature myeloid cells in MDS and CMPD. Mdm2 protein was expressed in 3/30 (10%) MDS in the immature myeloid cells and in 1/22 AML in blastic cells. The combined immunophenotypes of immature myeloid cells of MDS were: p53+/mdm2+/waf1-: 3, p53+/mdm2-/waf1-: 3, while the immunohistochemical patterns of AML were: p53+/mdm2-/waf1-: 4, p53+/mdm2+/waf1+: 1, p53+/mdm2-/waf1+: 1, p53-/mdm2-/waf1+: 3. Ki67/MIB1 staining was found in at least 30% of immature myeloid cells in MDS and AML and in at least 20% of these cells in CMPD. In conclusion, our results indicate that p53 protein is overexpressed in the myeloid lineage in a proportion of AML and MDS, while is not detected in CMPD and normal bone marrow, p53 expression was much more frequent in AML occurring as an evolution of MDS than in de novo AML. The combined immunophenotypes of p53 positive AML and MDS suggest that p53 overexpression may be due to mutation, in some AML and MDS cases with the p53+/mdm2-/waf1- phenotype. However, it would be also possible that p53 protein accumulation is not related to p53 mutation but to inhibition of p53/mdm2 binding due to mdm2 defects and/or other events related to cell stress signals. On the other hand, waf1/p21 protein overexpression without p53 expression in some AML could be p53-independent and may represent an attempt to control the high proliferation rate which was evidenced by Ki67/MIB1 immunostaining. However, the possibility of p21 to arrest cell-cycle, in these cases of AML, seems to be overridden, suggesting that cell-cycle deregulation may be involved in a proportion of AML. 相似文献
16.
胰腺癌p53上下游基因mdm2、p21WAF/CIP1以及P14ARF蛋白的表达及相互关系 总被引:14,自引:1,他引:14
目的 探讨p14ARF、p53、mdm2及p21WAF/CIP1蛋白在胰腺癌组织中的表达、相互关系及意义。方法 选取167例胰腺癌、101例癌旁与13例良性病变组织构建组织芯片(又称组织微阵列),应用免疫组织化学EnVision二步法检测这4种蛋白在胰腺良恶性病变中的表达。结果 p14ARF、p53、mdm12及p21WAF/CIP1在胰腺癌中表达的阳性率分别为35.3%(59/167)、57.5%(96/167)、64.1%(107/167)和39.5%(66/167)。同癌旁组织相比,p53和mdm2表达明显升高(P<0.01),而p14ARF和p21WAF/CIP1的表达明显降低(P<0.05)。p21WAF/CIP1的阳性表达与年龄、神经受累显著相关(P<0.05);p53的阳性表达与肿瘤的分化、淋巴结转移和神经受累均显著相关(P<0.05);mdm2的阳性表达与肿瘤的分化显著相关(P<0.05);p14ARF与年龄和浸润转移显著相关(P<0.05)。四者阳性表达两两之间统计学上具有关联性(P<0.05)。结论 p53和mdm2的过表达以及p14ARF和p21WAF/CIP1的缺失表达可能会导致胰腺癌的形成和进展;4种蛋白主要以p14ARF-p53-mdm2-p21WAF/CIP1通路的方式作用于细胞的转化和肿瘤的形成;联合检测p53和mdm2的表达可用于评定胰腺癌的恶性程度。 相似文献
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胃癌及胃液中p53、ras基因突变与临床病理的关系 总被引:3,自引:2,他引:3
目的:探讨胃良性病变向恶性转化过程中p53、ras基因突变的规律,并分析胃癌无损伤基因检测的可行性。方法:应用PCR-SSCP及免疫组织化学方法对比研究。结果:异型增生p53基因突变率10%(3/30)、ras基因突变率10%(3/30)、ras基因突变率16.7%(5/30)(二者总突变率26.7%);早期胃癌p53基因突变率35%(7/20)、ras基因突变率60%(12/20)(二者总突变率85%,其中2例重复突变); 中晚期胃癌p53基因突变率60%(18/30)、ras基因突变率43.3%(13/30)(二者总突变率90%,其中4例重复突变);胃息肉ras基因突变仅1/10。30例胃溃疡边缘正常黏膜均未发现p53、ras基因突变。p53基因突变的25例胃癌的胃液中其相应的突变率32%(8/25)。19例胃癌患者的胃液中9例有ras基因突变47.1%(9/19)。异型增生p53蛋白过度表达阳性率13.3%(4/30),p^21ras蛋白阳性率16.7%(5/30)。胃癌p53蛋白阳性率56%(28/50),p^21ras蛋白阳性率60%(30/50)。正常胃黏膜上皮、溃疡边缘正常黏膜及胃息肉均呈p53及ras蛋白阴性表达。结论:胃癌的发生发展与癌基因ras与抑癌基因p53的突变有关,且两种基因同时检测,可覆盖绝大多数胃癌病例,提高了本项技术的可靠性,提供了胃癌无损伤基因检测的可行性的实验证据。 相似文献
19.
We have previously reported the statistically significant correlation of immunohistochemical expression of MIB-1 and p53 proteins among benign, atypical, and anaplastic meningiomas and p53 protein expression was high in atypical and anaplastic meningiomas. In the present study, we analyzed 22 cases of meningiomas for mutation of p53 gene in its spectrum of exon 5 to 8 using automated genetic analyzer. We did not find any mutation of p53 in any of these cases, thus suggesting the p53 protein expression is wild type. We analyzed 72 cases of meningiomas for determining the methylation status of p14(ARF) gene and the immunohistochemical expression of MDM2 protein to explain p53 protein expression in these meningiomas. We found methylation of p14(ARF) gene in five of 58 cases of benign meningiomas (8.6%), two of 10 cases of atypical meningiomas (20%), and two of four cases of anaplastic meningiomas (50%). In absence of p53 gene mutation, the high percentage of p14(ARF) gene methylation in high-grade meningioma may have been responsible for accumulation of wild-type p53 protein. In addition, we also found the loss of MDM2 protein in high-grade meningiomas. These deregulations of p14-MDM2-p53 pathway may contribute to the malignant progression of meningioma. 相似文献
20.
We investigated a lipoma and a well-differentiated/dedifferentiated liposarcoma (WD/DDL), occurring simultaneously in one patient for the possible role of p53 and mdm2 in the molecular oncogenesis of liposarcoma and tumor progression. The hypothesis tested was if there is a continuum in the development from lipoma to liposarcoma. Lipoma was characterized by a lack of p53 mutation, p53 LOH and p53 protein expression, as well as by mdm2 amplification and mdm2 protein expression. p53 mutation and p53 LOH were found neither in the well-differentiated nor in the dedifferentiated parts of the liposarcoma. In contrast, mdm2 amplification and an increase in mdm2 protein expression were found to be associated with malignancy and dedifferentiation, whereas p53 protein expression was only slightly increased. These findings indicate that mdm2 constitutes one of the most common targets for molecular aberration in WD/DDL. We suggest that mdm2 is a marker distinguishing between ordinary lipoma and well-differentiated liposarcoma, and that the genesis of these tumors is different. 相似文献