P53和mdm2在骨巨细胞瘤中的表达

目的：探讨p53和mdm2在骨巨细胞瘤（GCT）的表达及与GCT病理分级和复发的关系。方法：应用SP免疫组织化学方法检测p53和mdm2在52例GCT（GCT按Jaffe分级：Ⅰ级15例、Ⅱ级25例、Ⅲ级12例）中的表达。结果：14例p53表达阳性,阳性率26．9％,18例mdm2表达呈阳性,阳性率达34．6％。其阳性表达与病理分级均无显著性差异（P值分别为0．699;0．871）。p53和mdm2在复发和无复发的病例中,阳性表达率分别为46．2％、20．5％和61．5％、25．6％。两者同时阳性表达有7例,p53和mdm2同时过表达与GCT复发有高度显著性差异（P＝0．008）。结论：p53和mdm2在GCT中的表达与病理分级无关而与其复发有关。     

p53和p21在骨巨细胞瘤中的表达及临床意义

目的：探讨p53和p21在骨巨细胞瘤（GCT）的表达及与GCT病理分级和复发的关系。方法：应用SP免疫组织化学方法检测p53,p21在52例GCT中的表达。结果：52例样本中,P53和P21的是性表达率分别为26．9％（14／52）和13．5％（7／52）,两者与病理分级无关（P值分别为0．6999,0．658）,在复发病例中,P53和P21的阳性率分别为46．2％和20．5％,在无复发病例中两者分别为23．1％和10．3％,两者同时表达阳性的有2例,p53和p21同时过表达与GCT复发有显著相关性（P=0\042),结论：p53和p21在GCT中的表达与病理分级无关,与复发相关。     

食管鳞癌组织中p53与p27及mdm2蛋白的表达及其意义

目的:探讨癌基因蛋白p53、p27及mdm2在食管鳞癌组织中的表达及其意义。方法:采用免疫组织化学EnVision二步法对85例食管鳞癌及其癌旁组织进行p53、p27及mdm2蛋白表达的检测。结果:85例食管鳞癌组织中p53阳性表达率为70·6%(60/85),癌旁组织为75·0%(39/52);p27与mdm2蛋白在癌组织中的阳性率分别为72·9%(62/85)和83·5%(71/85),明显高于癌旁组织的34·6%(18/52)和53·8%(28/52),P<0·05;且从鳞状上皮非典型增生→原位癌→鳞癌的发展过程中,p27蛋白的阳性表达率逐渐上升。p27蛋白阳性表达与组织学分级呈正相关,r=0·234,P<0·05;而mdm2阳性表达与组织学分级呈负相关,r=-0·272,P<0·05;三者阳性表达率均与浸润深度及淋巴结转移无关,P>0·05;p53与p27和mdm2蛋白的表达无相关性,P>0·05。结论:检测p53、p27及mdm2蛋白在食管鳞癌的表达有助于了解食管癌的发生发展以及推断临床预后。     

脑胶质瘤组织中MDM2、p53、p14ARF和p21WAF1蛋白表达及意义

[目的]探讨MDM2、p53、p14ARFF和p21WAF1九蛋白在胶质瘤组织中的表达及意义.[方法]应用免疫组化SP法检测胶质瘤组织中MDM2、p53、p14ARF和p21WAF1蛋白的表达情况,并分析其与胶质瘤组织学分级之间的关系.[结果]Ⅱ级和Ⅳ级胶质瘤中,MDM2阳性表达率分别为24.00%(6/25)及56.52%(13/23)(χ2=5.298,P=0.021);p53阳性表达率分别为28.00%(7/25)及60.87%(14/23)(χ2=5.259,P=0.022).p14ARF的阳性表达率分别为76.00%(19/25)及34.78%(8/23)(χ2=8.270,P=0.004),p21WAF1的阳性表达率分别为76.00%(19/25)及39.13%(9/23)(χ2=6.700,P=0.010).[结论]胶质瘤组织中,MDM2和p53均呈不同程度的过度表达,且随胶质瘤恶性程度的增加而表达水平增高,但p14ARF and p21WAF1蛋白随胶质瘤恶性程度的增加而表达降低.MDM2过表达、p53突变以及p14ARF、p21WAF1蛋白表达降低与胶质瘤的演进有关.     

鼻腔NK/T细胞淋巴瘤中p53相关蛋白和潜伏膜蛋白1的表达及其临床意义

目的 探讨鼠双微体2(mdm2)、p53、p21基因和潜伏膜蛋白1(LMP-1)在鼻腔NK/T细胞淋巴瘤(NKTL)中的表达及相互作用关系,以及其与NKTL临床分期和预后的关系.方法 收集62例NKTL患者的临床病理资料,并进行随访.取62例NKTL组织构建组织芯片,采用免疫组化SP法检测mdm2、pS3、p21及LMP-1蛋白的表达情况;应用原位杂交法检测EBER1/2的表达.结果 mdm2、p53、p21和LMP-1蛋白在NKTL中的阳性表达率分别为61.3%、79.0%、58.1%和48.4%,EBER1/2的阳性表达率为90.3%.随着肿瘤临床分期的进展,mdm2、p53和p21蛋白的阳性表达率逐渐升高,并与临床分期相关(均P<0.05).mdm2、p53和p21蛋白的表达呈正相关(P<0.05),其阴性表达组患者的预后均好于阳性表达组(均P<0.05).LMP-1蛋白的表达与临床分期和预后无关(P>0.05).p53蛋白的表达水平是NKTL的独立预后因素.结论 mdm2、p53、p21的蛋白表达与NKTL的发生和发展密切相关,可作为评估NKTL生物学行为的良好指标.p53蛋白的表达水平是NKTL的独立预后因素.     

EB病毒相关胃癌与mdm2，p53及p21基因异常的研究

 目的 探讨p53基因突变以及mdm2，p53和p21蛋白表达异常在EBV相关胃癌（EBVaGC）发生发展中的作用。方法 应用免疫组化技术检测13例EBVaGC、45例临床病理资料与之匹配的EBV阴性胃癌（EBVnGC）组织中 mdm2，p53和p21蛋白的表达；PCR-SSCP银染技术结合DNA序列分析检测p53基因exon 5~8突变；RT-PCR检测EBV相关基因的表达。结果 E-BVaGC组与EBVnGC组相比，两组间mdm2，p53和p21蛋白的阳性检出率差异无统计学意义（P = 0.830 0；P = 0.791 2；P = 0.353 1），但EBVaGC组p53蛋白过表达率（15.38 %）明显低于EBVnGC组（57.78 %），两组间差异有统计学意义（P = 0.008 5）。mdm2蛋白阳性表达与p53蛋白过表达呈显著正相关（P = 0.000 8，r = 0.439 1）；p21与p53蛋白共同表达率较高，但经计数资料相关性统计学分析表明两者无显著相关性（P = 0.2501，r = 0.202 5）。2例EBVnGC检测到p53基因突变，突变均位于exon 5，13例E-BVaGC和58例相应癌旁组织均未检测到p53基因突变。13例EBVaGC核抗原基因EBNA1均为阳性，潜伏膜蛋白基因LMP1均为阴性，即刻早期基因BZLF1，早期基因BARF1和BHRF1阳性率分别为46.15 %（6／13），46.15 %（6／13）和15.38 %（2／13），三者与EBVaGC组织中mdm2，p21和p53蛋白的表达均无显著相关性（P＞0.05）。 结论 EBV感染以及mdm2，p53和p21蛋白表达异常与胃癌发生有关； p53基因突变可能并非胃癌组织中p53蛋白异常累积的主要原因；胃癌组织中EBV感染与p53蛋白的异常表达有关，而与mdm2和p21蛋白的异常表达以及p53基因突变无显著相关性。     

膀胱移行细胞癌中MDR、p53表达及细胞凋亡的意义

目的:探讨膀胱移行细胞癌(BTCC)中P-gP、p53基因及细胞凋亡表达的意义.方法:利用免疫组化S-P法和TUNEL法检测83例BTCC的P-gP、p53的表达及细胞凋亡指数(AI).结果:在83例膀胱移行细胞癌中P-gp阳性表达率为71.08%,p53阳性表达率为50.60%,AI为1.4335±0.3863;P-gp阳性表达在不同病理分级、临床分期及预后中无显著性差异(P＞0.05),p53及AI随着病理分级和临床分期而增高,均有显著性(P＜0.05),p53阳性表达复发组高于无复发组(P＜0.01),AJ复发组高于无复发组(P＜0.05).结论:检测P-gp可指导BTCC的化疗药物选择,p53高表达、细胞凋亡指数增高与BTCC的进展有关,P-gp、p53及AI高表达者预后及疗效差,p53可作为BTCC独立的预后因素.     

Her-2/neu、p53和P-gp在非小细胞肺癌中的表达

[目的]探讨非小细胞肺癌（NSCLC）中Her-2/neu、p53和P-gp的表达及临床意义。[方法]采用免疫组化EnVision法,对60例NSCLC及其20例正常肺组织中Her-2/neu、p53和P-gp进行检测。[结果]Her-2/neu、p53和P-gp相关蛋白在NSCLC中的表达分别是75%、70%和75%,而正常组织未见表达（P均〈0.01）。Her-2/neu的表达与病理类型和组织学分级呈相关性（P=0.031和P=0.047）;p53的表达与淋巴结转移、临床分期有关（P=0.024和P=0.003）;P-gp的表达与病理类型有关（P=0.020）;三者之间,Her-2/neu的阳性表达与p53和P-gp的阳性表达存在明显正相关性（P=0.025和P=0.000）,而p53的阳性表达与P-gp的阳性表达之间未见明显相关性（P=0.517）。[结论]Her-2/neu、p53和P-gp在NSCLC的发展过程中起了重要作用,联合检测该三项基因的表达将有助于判断是否存在肿瘤的原发耐药及治疗方案的选择。     

骨巨细胞瘤p53、c-myc表达

[目的]探讨骨巨细胞瘤p53、c鄄myc的表达与骨巨细胞瘤临床分期及复发之间的关系。[方法]对75例骨巨细胞瘤标本,采用免疫组织化学法检测p53、c鄄myc蛋白的表达,分析其与骨巨细胞瘤临床病理特性的关系。[结果]骨巨细胞瘤p53、c鄄myc的表达率分别为28%、24%。p53、c鄄myc的表达与Enneking’s外科分期有关(P<0.05)。p53表达阳性组复发率明显高于阴性组(P<0.05)。c鄄myc表达与p53表达有显著相关性(P<0.05),且p53(+)/c鄄myc(+)组肿瘤复发率明显高于单一阳性组及双阴性组(P<0.05)。[结论]p53、c鄄myc的表达与骨巨细胞瘤的恶性程度及复发有关,可作为判定骨巨细胞瘤恶性程度、复发潜能及指导临床治疗的参考指标。     

mdm2、p53在胶质瘤中的表达意义及与临床病理特征的关系

目的:分析mdm2、p53在胶质瘤中的表达意义及与临床病理特征的关系。方法:选取我院2012年4月至2013年4月期间存档的54例胶质瘤石蜡标本以及相应瘤旁正常组织标本作为研究对象，将胶质瘤石蜡标本作为观察组，将瘤旁正常组织标本作为对照组。采用LSAB免疫组化法测量两组样本中mdm2、p53蛋白表达水平，分析上述蛋白在胶质瘤患者疾病发生及发展中的具体意义。结果:胶质瘤石蜡标本中mdm2、p53阳性表达率显著高于相应瘤周正常组织标本（P＜0.05）；Ⅲ、Ⅳ期胶质瘤患者p53、mdm2阳性表达率及“+++”表达率显著高于Ⅰ、Ⅱ期患者（P＜0.05）；p53、mdm2高表达患者术后生存时间均显著低于p53、mdm2低表达患者（P＜0.05）；p53、mdm2阳性表达率均与疾病分期以及淋巴结转移有明显相关性（P＜0.05）；mdm2、p53蛋白在胶质瘤中呈正相关（r=0.713，P＜0.05）。结论:mdm2通过调节p53蛋白的表达对胶质瘤发生发展起调控作用，Ⅲ、Ⅳ期疾病分期及淋巴结转移等因素均对mdm2、p53在肿瘤细胞中的异常表达有相关性，临床中可针对上述指标阳性表达程度预测患者病情发展，并为后续治疗方案的制定及改善提供相应的数据支持。     

Expression of p21/waf1 in oral squamous cell carcinomas--correlation with p53 and mdm2 and cellular proliferation index

The cyclin-dependent kinase inhibitor p21/waf1 is regulated by p53-dependent and p53-independent pathways. In addition, mdm2 is an oncogene which forms an auto-regulatory loop with the normal p53 protein and its role has been implicated in oncogenesis. To determine whether a correlation exists between the expression of these gene products, tumor differentiation, tumor staging and radiation therapy, we investigated the expression of p21, p53 and mdm2, and cellular proliferation by Ki-67 (MIB1) labeling index using immunohistochemistry in 88 human oral squamous cell carcinoma (SCC) samples from 56 patients. Tumor expression of all nuclear proteins was scored according to the percentage of positive cancer nuclei, both with the cancer tissue as a whole as well as in different epithelial compartments of differentiation. Positive p21, p53, mdm2 and MIB1 staining was present in 82.4, 67.8, 25.9 and 98.8% of the SCC samples. The staining in different epithelial compartments of differentiation varied: those of p21 and mdm2 present predominantly in suprabasal and upper regions of the tumors: those of p53 and MIB1 in basal and suprabasal regions. Higher levels of p21 expression were seen in actively proliferating tumors (P = 0.025). p21 expression positively correlated with mdm2 expression but not with p53 expression. Moreover, the level of p21 expression was higher in older patients (P = 0.024) and female patients (P = 0.008). There was no significant association among p53, mdm2 and MIB1. Expression of p53 was higher in tumors with poorer cellular differentiation and in younger patients (P = 0.038 and 0.028). There was no association between tumor stage by TNM classification and the expression of any of these gene products or proliferation index. Radiation therapy did not alter the expression of any of these. To conclude, p21 protein was overexpressed in oral SCCs, and this overexpression was related to cell proliferation index and mdm2 expression but independent of p53 protein alteration. Overexpression of p21 alone appeared to be insufficient to suppress tumor progression.     

Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally advanced bladder carcinoma

BACKGROUND: The aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma. METHODS: The hospital records from all 173 patients treated with cystectomy for locally advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively reviewed. Three consecutive sections from biopsies taken before any treatment were stained using the standard immunohistochemical technique for p53, p21, and mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression and 10% or more for positive p21 and mdm2 expression. RESULTS: Positive immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors (51%), and for mdm2 in only 16 tumors (9%). The only association found between immunostaining for the three antibodies was that most mdm2-positive tumors had positive p21 expression. Tumor mapping of regional immunostaining showed no association between immunostaining for p53 and p21. In a proportional hazards analysis, no association was found between the results of immunostaining for the three antibodies and treatment outcome. CONCLUSIONS: Positive or negative expression of p53, p21, or mdm2, or combinations of these, was not associated with cancer specific mortality after cystectomy for bladder carcinoma. There was no association between immunostaining for p21 and p53, whereas positive immunostaining for mdm2 was observed in a minority of the tumors. These results indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins and tumor suppressor proteins along the p53 pathway that are involved in tumor development and progression.     

mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters.

The present study was designed to analyze the expression of p53 and mdm2 in clear cell renal cell carcinoma with special emphasis on their association with tumor grade and clinical outcome. In particular, the value of individual protein overexpression as well as combined p53/mdm2 positivity was evaluated because both proteins are functionally connected, and their expression is controlled by an autoregulatory feedback loop. A cohort of 97 clear cell renal cell carcinomas was analyzed. The overexpression of mdm2 and p53 proteins was investigated on paraffin-embedded material by using monoclonal antibodies. Eighteen tumors showed mdm2 positivity, whereas 35 of the tumors overexpressed p53. Whereas p53 and mdm2 positivity correlated significantly (P = 0.00004), no correlation could be found between mdm2 protein overexpression and tumor stage, lymph node involvement, and presence of distant metastases. mdm2 positivity was found significantly more frequently in tumors of higher grade. In univariate analysis, there was a statistically significant correlation between p53 and mdm2 overexpression in the same tumor and poor survival (P = 0.00179). Multivariate analysis revealed that coincident mdm2/p53 overexpression, the presence of distant metastases, and tumor grade were independent predictors for tumor progression. Our results indicate that mdm2/p53 co-overexpression, nuclear grade, and preoperative presence of distant metastasis are independent predictors for poor survival.     

骨巨细胞瘤中 nm23 和 ras 基因的表达及临床意义

目的 :探讨nm2 3和ras基因在骨巨细胞瘤 (GCT)的表达及与GCT病理分级和复发的关系。方法 :应用SP免疫组织化学方法检测nm2 3和ras在 52例GCT (GCT按Jaffe分级 :Ⅰ级 15例、Ⅱ级2 5例、Ⅲ级 12例 )中的表达。结果 :2 1例nm2 3表达阳性 ,阳性率 4 0 .4 % ,7例ras表达呈阳性 ,阳性率13.5%。其阳性表达与病理分级均无显著相关性 (P >0 .0 5)。nm2 3和ras在复发和无复发的病例中 ,阳性表达率分别为 6 9.2 %、30 .8%和 2 3.1%、10 .3%。nm2 3过表达与GCT复发有高度相关性 (P <0 0 5)。而ras基因表达无相关性。结论 :nm2 3和ras表达均与GCT病理分级无关。nm2 3表达与肿瘤复发有关 ,而ras表达与复发未见相关性