胃癌患者p53基因甲基化的研究

作者应用限制性内切酶ＨｐａⅡ和ＭｓｐⅠ酶切胃癌组织及正常胃组织ＤＮＡ，经ＰＣＲ扩增ｐ５３基因第５外显子，琼脂糖凝胶电泳分析其电泳图谱，比较胃癌组织及正常胃组织ｐ５３基因第５外显子特定序列５′－ＣＣＧＧ－３′位点甲基化差异。结果显示：１５例胃癌组织中１２例ｐ５３基因第５外显子出现高甲基化状态，而１０例正常胃组织为低甲基化状态，结果提示，ｐ５３基因高甲基化状态与胃癌发生有关。     

抑癌基因p53在胃癌组织的表达及临床意义

目的：探讨ｐ５３基因在胃癌的表达与临床、病理因素及预后的关系,探索ｐ５３基因异常表达在胃癌发生过程中的作用。方法：使用抗ｐ５３蛋白单克隆抗体ＤＯ－７,对９９例人胃癌组织ｐ５３的表达进行免疫组化研究。结果：４８例胃癌组织ｐ５３基因表达阳性（４９％）。ｐ５３基因表达与胃癌的大体类型、分化工、淋巴结转移等指标均无明显关系。在１０例不典型增生的癌旁组织中,２例呈阳性反应;在４例有肠上皮化生的癌旁组织中及其     

胃癌中hMSH2、p53和PCNA表达的相关性及意义

目的:探讨胃癌中hMSH2、p53和PCNA表达的相关性及意义.方法:采用免疫组织化学SP法,检测胃癌、癌旁和胃炎粘膜中hMSH2、p53和PCNA表达情况.结果:1)3种基因产物在胃癌中的阳性率均显著高于非癌组织,其中,p53和PCNA在低分化癌中的阳性率显著高于高分化癌,有淋巴结转移者显著高于无转移者(P＜0.05).2)胃癌中hMSH2/PCNA及p53/PCNA表达均呈正相关(P＜0.05).结论:hMSH2、p53和.PCNA的异常表达及hMSH2与PCNA之间的相互调节可能与胃癌的发生发展密切相关.     

p53蛋白表达对不同部位大肠癌患者预后判断的价值

目的　探讨p5 3蛋白过度表达对不同部位大肠癌患者预后判断的价值。方法　应用免疫组化方法检测 75例大肠癌组织中 p5 3蛋白表达情况。 结果　p5 3蛋白表达阳性率为 46.7% (3 5 / 75 )。远侧大肠癌 p5 3蛋白表达率 (5 9.5 % )显著高于近侧者(3 0 .3 % ) (P <0 .0 5 )。p5 3蛋白表达与其它临床病理因素无明显相关。全组中位数随访时间为 60个月 ,p5 3蛋白表达阳性与阴性患者术后总生存率比较有显著性差异 (P <0 .0 5 )。在远侧大肠癌组织中 p5 3阳性患者的预后明显差 (P <0 .0 1)。而在近侧大肠癌中 ,2组患者的预后则无显著性差异 (P >0 .0 5 )。结论　不同部位大肠癌 p5 3蛋白表达存在一定差异 ,p5 3蛋白过度表达对远侧大肠癌患者预后判断有重要作用     

Ki67、p53及EGFR在胃癌组织中的表达水平及临床意义

目的 探讨Ki67、p53及EGFR在胃癌组织中的表达水平及其临床意义.方法 收取行病理学检查的胃癌患者170例作为研究对象,对其胃癌组织及癌旁组织的石蜡切片进行ki67、p53及EGFR免疫组化染色.结果 胃癌组织中Ki67、p53及EGFR阳性表达率分别为71.18%、55.88%及45.29%;癌旁组织中Ki67、p53及EGFR阳性表达率分别为31.76%、12.94%及10.59%.胃癌组织阳性表达率均明显高于癌旁组织,差异具有统计学意义(P<0.05).3种指标均与肿瘤浸润深度、分化程度、淋巴结转移以及TNM分期密切相关,即随着肿瘤进展而其阳性率增高(P<0.05).Ki67与p53、EGFR均呈正相关(P<0.05);p53与EGFR相关性不显著(P>0.05).结论 Ki67、p53及EGFR与胃癌的发展关系密切,均可作为判断胃癌恶性程度及进展情况的可靠指标.     

胃癌P53基因表达及其与淋巴组织增生关系的研究

对82例胃癌作了S－P法免疫组化染色，观察p53癌基因在各型胃癌中的表达以及与其淋巴组织增生之间的关系。结果癌周淋巴细胞浸润的程度，癌引流区淋巴结反应性增生的数量与p53蛋白表达呈负相关；癌引流区淋巴结癌转移及其分期与p53蛋白表达呈正相关，p53阳性表达与胃癌组织学类型，分化程度无明显关系。     

胃癌p53和nm23基因异常表达的预后意义研究

目的研究胃癌ｐ５３和ｎｍ２３基因异常表达与胃癌生物学行为及病人预后的关系。方法采用链霉素—生物素（ＳＰ）免疫生化技术行ｐ５３和ｎｍ２３免疫组化染色,研究了２０９例胃癌病人的临床病理资料。结果ｐ５３和ｎｍ２３基因的异常表达率分别为４９．７６％和５７．４２％,ｐ５３及ｎｍ２３异常表达与病人性别、年龄、肿瘤部位、大小无关。随着ＴＮＭ分期的进展ｐ５３基因异常表达率升高（Ｐ＝０．００９）,Ｂｏｒｍａｎｎ４胃癌ｎｍ２３异常表达率高（Ｐ＝０．０２６）,ｐ５３在粘液腺癌低表达（Ｐ＝０．０１８６）,ｐ５３及ｎｍ２３与胃癌的淋巴结转移有关（Ｐ＝０．０１８,Ｐ＝０．００２）。ｐ５３及ｎｍ２３与术后生存时间有关。结论ｐ５３及ｎｍ２３基因异常表达能反映胃癌的生物学行为,并与胃癌的预后有关。ｎｍ２３更能提示胃癌转移,但ｐ５３提示预后的能力比ｎｍ２３强。     

胃粘膜异型增生上皮p53蛋白表达的临床意义

采用免疫组化方法，对２４例常规胃镜活检的胃粘膜异型增生上皮的ｐ５３蛋白表达进行检测，并做１～２４个月的随访研究。结果表明，ｐ５３蛋白阳性的异型增生上皮的癌检出率为５７．１％（４／７），其中２例为早期胃癌，而ｐ５３阴性的异型增生上皮的癌检出率为１１．８％（２／１７），两者有显著性差异（Ｐ＜０．０５）。结果提示，胃粘膜上皮ｐ５３蛋白表达是一项恶性生物学指标，可作为早期诊断及鉴别诊断胃癌的标志     

No Evidence of Association of the Arg72Pro p53 Gene Polymorphism with Cancer Risk in the Saudi Population: a Meta-Analysis

Background: Earlier studies on the association between p53 codon 72 Arg>Pro polymorphism and cancerrisk were inconclusive and conflicting for the Saudi population. Therefore, we performed a meta-analysis toinvestigate the relationship between the codon 72 Arg>Pro polymorphism and overall cancer risk in SaudiArabia. Materials and Methods: We searched all eligible published studies and data were pooled together toperform the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculatedfor homozygous, heterozygous, dominant and recessive genetic models. Results: A total of five eligible publishedstudies covering 502 cancer cases and 784 healthy controls were included in the meta-analysis. No publicationbias was detected in this study. The results suggested that the variant (Pro vs Arg: p=0.960; OR=1.004, 95%CI=0.852-1.183), homozygous (Pro.Pro vs Arg.Arg: p=0.970; OR=1.006, 95% CI=0.729-1.390), heterozygous(Arg.Pro vs Arg.Arg: p=0.473; OR=0.783, 95% CI=0.402-1.527) carriers were not associated with overall cancerrisk. Similarly, dominant (Pro.Pro+Pro.Arg vs Arg.Arg: p=0.632; OR=0.886, 95% CI=0.540-1.454) and recessive(Pro.Pro vs Pro.Arg+Arg.Arg: p=0.269; OR=1.163, 95%CI=0.890-1.521) models also did not indicate increasedrisk of cancer. Conclusions: The current meta-analysis suggests that the codon 72 Arg>Pro polymorphism ofthe p53 gene might not contribute to cancer susceptibility in Saudi population. Future well designed large casecontrol studies are needed to validate our findings.     

检测肺癌患者血清p53抗体的临床意义

目的:探讨检测肺癌患者血清p53抗体的临床意义。方法:采用酶联免疫吸附法检测120例肺癌患者血清p53抗体,并以30例肺部良性疾病患者和120例正常健康人作对照。结果:肺癌患者血清p53抗体水平明显高于肺部良性疾病患者和正常人(P<0.05),而正常人与肺部良性疾病患者间无显著性差异(P>0.05)。120例肺癌中26例p53抗体阳性,阳性率为21.7%,而30例肺部良性疾病患者和120例正常人无1例阳性。肺癌者血清p53抗体与肺癌细胞分化程度和临床分期有密切关系(P<0.01)。结论:检测血清p53抗体水平有助于肺部良恶性疾病的诊断及鉴别诊断。     

p53,ras,nm23在原发性胃癌中的联合表达研究

应用免疫组化ABC法，检测78例原发性胃癌组织P53、p21（ras基因表达产物）和nm23基因蛋白的表达，探讨其与肿瘤发展、分化程度、淋巴结转移等胄癌生物学行为的关系。结果p53在中晚期胄癌（57％）、低分化胃癌（76％）、伴淋巴结转移胃癌（62％）中的表达明显高于其在早期（1％）、高分化（4％）反不伴淋巴结转移胄癌（20％）中的表达率（P＜0．05）；p21蛋白表达与胃癌分期和有无淋巴结转移的关系也显示了类似趋势，但其与分化程度的关系无统计学意义；nm23表达主要与癌细胞侵袭程度和淋巴结转移呈负相关（P＜0．05），不同分化程度胄癌中的表达无显著差异。结果表明：胃癌的发生、发展可能与多基因异常有关，p53、p21高表达与nm23低表达在癌细胞增殖及肿瘤浸润中起重要作用，胃癌淋巴结转移是一个多基因作用且较为复杂的过程。     

胃癌、癌前病变组织中p53蛋白表达的临床意义

目的探讨胃癌及癌前病变组织中p53蛋白表达的临床意义.方法采用间接免疫荧光标记染色和流式细胞术,检测并比较10例正常胃粘膜、13例浅表性胃炎、10例肠上皮化生、11例不典型增生及16例胃癌组织中p53蛋白的表达水平.以DNA指数、增殖指数(PI)、荧光指数(FI)为分析指标.结果胃癌、不典型增生及肠上皮化生的FI值分别为1.866±0.096、1.143±0.060、1.050±0.074,与正常胃粘膜(0.602±0.077)比较,均有显著性差异(P＜0.05),与浅表性胃炎(0.898±0.052)比较,也有显著性差异(P＜0.05).胃癌组织的FI值高于不典型增生及肠上皮化生(P＜0.05).不典型增生组织p53蛋白阳性率为25.0%(2/8),胃癌为68.4%(13/19),在不典型增生及胃癌组织中,其异倍体的FI值、PI值和p53蛋白阳性率与二倍体者比较,均有显著性差异(P＜0.05).结论胃癌组织p53蛋白的表达水平高于癌前病变及正常胃粘膜组织;随病变向恶性转化,p53蛋白表达水平、PI值及异倍体率均增高.因此,检测p53蛋白表达水平对胃癌的诊断具有一定意义.     

p53 and BCL-2 as Prognostic Markers in Endometrial Carcinoma

The objective of this study was to verify the frequency of p53 and BCL-2 immunohistochemical expression in patients with endometrial carcinoma and to correlate it with histological factors (histological type, tumor grade, depth of myometrial invasion, lymph node involvement and surgical staging) and survival. Forty-eight patients with endometrial carcinoma who were submitted to primary surgical treatment were assessed. p53 and BCL-2 immunohistochemical expression was determined using paraffin blocks containing the tumor area. p53 and BCL-2 expression was detected in 39.6% and 58.3% of the tumors, respectively. No significant difference was found regarding the frequency of p53 expression when analyzing histological type (33.3% in endometrioid tumors, 58.3% in non-endometrioid tumors; p = 0.176), depth of myometrial invasion (p = 0.632) and surgical staging (I—11.1%, II—66.7%, III—57.1%; p = 0.061). p53 expression was significantly more frequent in undifferentiated tumors (p = 0.007) and in those showing lymph node involvement (p = 0.030). Univariate analysis showed a positive association with death (RR, 3.358; CI, 1.386–8.134; p = 0.005) and short-term survival. The present study did not reveal any correlation between BCL-2 expression and histopathologic markers or survival. In conclusion, this study showed that p53 expression is directly correlated with undifferentiated tumors, lymph-node involvement and risk of death. On the other hand, BCL-2 expression was not correlated with any known histological factors.     

p53 蛋白过度表达与胃癌生物学行为关系的探讨

采用ＡＢＣ免疫组织化学方法，检测７２例原发性胃癌ｐ５３表达变化，探讨肿瘤抑制基因ｐ５３蛋白过度表达与胃癌生物学行为的关系。结果ｐ５３阳性染色率为５１．４％（３７／７２），其过度表达与肿瘤浸润深度、淋巴结转移及肿瘤的分化程度呈正相关（Ｐ＜０．０５）。ｐ５３阳性肿瘤淋巴结转移率为８６．０％，ｐ５３阴性肿瘤的淋巴结转移率为６０％，前者明显高于后者（Ｐ＜０．０５）。进一步观察显示ｐ５３过度表达与胃癌的分化程度有明显的相关性，其在高、低分化胃癌中的表达率分别为３９％、７８％，两者差异显著（Ｐ＜０．０５）。结果表明ｐ５３在胃癌发生发展中可能起着重要的作用，检测ｐ５３可作为预后判断的有效指标。     

Mutations in Zinc-binding Domains of p53 as a Prognostic Marker of Esophageal-cancer Patients

Some investigators have suggested that mutations of the p53 gene may be molecular markers for poor prognosis of cancer patients, although others have reported conflicting results. We examined esophageal cancers from 138 patients to investigate whether mutational status of p53 could be correlated either with prognosis or with response to chemotherapy or radiation. We detected p53 mutations in the tumors of 78 (56.5%) patients. Kaplan-Meier analysis showed that these 78 patients tended to have shorter survival times and greater resistance to either form of therapy than patients whose tumors carried two wild-type p53 alleles. The difference became more evident when we focused on mutations in zinc-binding domains of p53 (L2 and L3); the prognosis was significantly poorer among the 29 patients with tumors in this category than among patients whose tumors had no p53 mutations, or p53 mutations outside L2 or L3 ( P =0.0060). Moreover, those tumors as a group were more resistant to chemotherapy or radiation than the others ( P =0.0105). Our results underscore the importance of the zinc-binding domains of p53 with respect to clinical prognosis for patients with esophageal carcinomas.     

贲门癌组织中P-糖蛋白和p53蛋白的表达及其意义

目的　探讨贲门癌组织中P -糖蛋白 (p -gp)和p5 3蛋白共同表达的临床意义 ,研究其与贲门癌生物学行为的关系。方法　采用免疫组化方法 (二步法 )检测 66例术前未经化疗的贲门癌组织中多药耐药基因产物P -糖蛋白和 p5 3蛋白的表达情况。结果　P -gp和 p5 3在贲门癌组织中表达率分别为 3 6.4% (2 4/66)和 5 1.5 % (3 4/66)。P -gp表达与贲门癌组织学类型、临床分期和淋巴结转移均无关 (P >0 .0 5 ) ;p5 3除与淋巴结转移有关外 (P <0 .0 5 ) ,与其组织学类型和临床分期均无关 (P >0 .0 5 )。p5 3表达阳性病例P -gp表达率明显高于 p5 3表达阴性病例 ,即 83 .3 %P -gp阳性表达患者 p5 3表达阳性。 结论　P -gp和 p5 3常共同表达于贲门癌组织中 ,可作为判断贲门癌患者预后和临床耐药的 1个可靠指标     

p53和p21基因蛋白表达与胃癌侵袭力的关系

采用免疫组织化学方法研究了６８例胃癌中癌细胞ｐ５３和ｐ２１基因蛋白表达与癌细胞侵袭力的关系。结果表明：６８例胃癌中有３６例ｐ５３基因蛋白染色阳性（５２．９％）,４８例ｐ２１基因蛋白染色阳性（７０．６％）;浸润于浆膜层和肌层的癌细胞ｐ５３蛋白染色的阳性程度明显高于粘膜层癌细胞（Ｐ＜０．０５）;浸润性生长的癌细胞中ｐ５３和ｐ２１蛋白阳性程度均明显强于膨胀性生长的癌细胞（Ｐ＜０．０５）;淋巴结转移病例的癌细胞其ｐ５３和ｐ２１蛋白染色阳性率（分别为５４．３％和７３．９％）与无淋巴结转移的病例（分别为５０．０％和６３．６％）无显著性差异（Ｐ＞０．０５）;有淋巴结转移的病例中,原发癌ｐ５３蛋白阳性强度与转移癌正相关（γ＝０．６８,Ｐ＜０．０１）。结果提示：ｐ５３和ｐ２１基因蛋白染色阳性程度较高的胃癌细胞具有较强的侵袭力。     

胰腺癌中p21ras、p53蛋白及PCNA的检测和临床意义

 目的　探讨p21ras、p53蛋白和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在胰腺癌发生、发展中的作用和临床意义。方法　应用免疫组化法对30例胰腺癌,3例正常胰腺组织中的ras基因产物p21、p53蛋白和PCNA进行检测,并结合临床资料分析。结果　胰腺癌中p21、p53蛋白表达正相关,阳性表达率分别为75%、53.33%;PCNA阳性表达率为43.39%±17.99%,并随胰腺癌恶性度的增加而增加,与预后、p53表达相关(P<0.05),与淋巴结转移、神经侵润及肿瘤大小无关(P>0.05)。结论　胰腺癌的发生发展过程是多种癌基因协同作用的结果;PCNA可作为判定胰腺癌恶性程度及预后的一项指标。     

Prognostic Significance of Beclin-1 Expression in Colorectal Cancer: a Meta-analysis

Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers.However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed toevaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients.Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer andChinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed todetermine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were includedin our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associatedwith poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overallsurvival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was noevidence of publication bias as suggested by Egger’s tests for tumor distant metastasis (p=1.000), differentiation(p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expressioniss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as anefficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.     

p53在喉癌中的免疫组化研究及临床意义

本文用ABC免疫组化方法，以抗p53单抗对70例喉良恶性标本研究，探讨p53与喉癌生物学行为及预后的关系。结果表明：p53蛋白在喉癌中的阳性表达率为64．7％，p53蛋白在良性病变中无表达。p53蛋白表达与喉癌病理分级、淋巴结转移、吸烟及预后相关；而与临床分期、年龄及生长部位无关。