细胞凋亡相关基因p53、bcl-2 mRNA表达与喉鳞癌关系的研究

目的 探讨细胞凋凋亡相关基因p53、bcl-2mRNA表达与喉鳞癌发生、发展,临床病理及分期分型的关系。方法 采用原位杂交技术（in situ hybridization)对60例喉鳞癌及8例声带息肉标本进行突变型p53、bcl-2mRNA检测。结果 60例喉鳞癌中p53、bcl-2mRNA阳性表达率分别为66.7%和48.3%,8例声带息肉全部为阴性,p53、bcl-2mRNA表达与喉鳞癌分化程度及颈淋巴结转移有关,而与喉鳞癌的临床分期分型无关。结论 p53、bcl-2基因可能参与了喉鳞癌细胞凋亡的调节,在叫做鳞癌的发生、发展和凋亡抑制过程中可能起着重要的作用。     

乳腺癌中bcl-2表达与p53和雌激素受体关系的研究

目的　研究乳腺癌中bcl- 2基因表达与p5 3基因和雌激素受体的关系以及对乳腺癌生物学行为影响。方法　应用S -P免疫组织化学方法对 4 5例乳腺癌石蜡包埋组织进行检测。结果在人的乳腺癌中bcl- 2、p5 3蛋白和雌激素受体阳性表达率分别为 5 5 5 %、5 1 1%和 4 6 7%。bcl- 2阳性表达与肿瘤大小、淋巴结是否发生转移无关 (P >0 0 5 ) ;与p5 3阳性表达呈负相关 (P <0 0 5 ) ;与乳腺癌恶性程度和雌激素受体阳性表达呈正相关 (P <0 0 5 )。结论　bcl- 2基因、p5 3基因和雌激素共同参与了乳腺癌的发生和发展 ;bcl- 2阳性表达常会减弱p5 3的表达 ;为综合评价bcl- 2基因在乳腺生物学行为中的作用提供了一些线索。     

bcl-2、p53表达与乳腺癌预后的关系

目的：探讨ｂｃｌ２ 、ｐ５３ 表达与乳腺癌预后的关系。方法：应用免疫组化ＬＳＡＢ法检测６４ 例乳腺癌及３０ 例乳腺良性病变的表达。分析ｂｃｌ２、ｐ５３ 与乳腺癌组织学分级、腋淋巴结转移、复发和预后的关系。结果：ｂｃｌ２ 与ｐ５３ 表达之间差异有显著性,呈负相关（ Ｐ＜ ０－０５） 。ｂｃｌ２ 和ｐ５３ 表达与组织学分级有关（ Ｐ＜ ０－０５） ,ｂｃｌ２ 表达随分级增加阳性率降低,ｐ５３ 则相反。ｐ５３ 表达与腋淋巴结转移有关（ Ｐ＜ ０－０５） 。ｂｃｌ２ 表达与腋淋巴结转移无关（ Ｐ＞ ０－０５） 。ｐ５３ 表达复发组明显高于无复发组（ Ｐ＜０－０５）;ｂｃｌ２ 表达与有无复发无关（Ｐ＞０－０５）。ｐ５３ 表达阳性率≤５ 年生存组明显高于＞ ５ 年生存组,呈负相关（ Ｐ＜ ０－０５）;ｂｃｌ２ 表达与生存期无关（Ｐ＞ ０－０５） 。结论：ｂｃｌ２ 表达与预后无关,其阳性表达可反映肿瘤属分化较好或属早期阶段。ｐ５３ 可单独作为预后指标;ｐ５３ 表达与预后呈负相关。     

p53、p16及HER-2蛋白在子宫内膜癌组织中的表达及与临床病理特征的关系研究

目的:研究分析子宫内膜癌组织中p53、p16及HER-2蛋白表达与患者临床病理特征之间的关系.方法:选取我院2017年6月至2021年3月收治的70例经术后病理学检查确诊的子宫内膜癌患者作为研究对象.采用免疫组化法对患者病理组织中p53、p16及HER-2蛋白表达进行检测,并分析这三种蛋白的表达与癌症发生、病理类型、分化程度、FIGO分期的关系.结果:与癌旁组织相比,癌组织p53及HER-2阳性率更高(P<0.05),p16阳性率更低(P<0.05);p53、p16以及HER-2在腺癌与非腺癌组织中的阳性率无明显差异(P>0.05);p16阳性率在G2级患者组织中最高,G3级次之,G1级患者组织中最低(P<0.05),p53、HER-2阳性率在G1级患者组织中最高,G2级次之,G3级患者组织中最低(P<0.05);与Ⅰ期、Ⅱ期患者相比,Ⅲ期、Ⅳ期患者p53、HER-2阳性率均更高(P<0.05),而p16阳性率更低(P<0.05);子宫内膜癌组织分级和分期与p53、HER-2阳性表达为正相关关系(P<0.05),与p16阳性表达为负相关关系(P<0.05).结论:子宫内膜癌患者临床病理特征与p16表达降低及p53、HER-2表达升高存在明显相关性,可为临床治疗及患者预后评估提供依据和参考.     

胶质瘤p53、bcl-2、MDM2表达与细胞增殖和凋亡的关系

目的：研究胶质瘤中ｐ５３ 、ｂｃｌ２ 、ＭＤＭ２ 表达与细胞增殖和凋亡的关系。方法：对４８ 例胶质瘤用免疫组化法检测ｐ５３、ｂｃｌ２、ＭＤＭ２ 蛋白表达;以Ｋｉ６７ 标记指数和ＡｇＮＯＲ 计数检测其增殖活性;用ＴＵＮＥＬ 法检测细胞凋亡。结果：ｐ５３、ｂｃｌ２、ＭＤＭ２ 蛋白表达阳性率分别为４７－９ ％ 、３５－８ ％ 及１２－５ ％ ,细胞增殖活性随肿瘤ｐ５３ 、ｂｃｌ２、ＭＤＭ２ 表达水平增高而增高,细胞凋亡则相反。结论：ｐ５３、ｂｃｌ２、ＭＤＭ２ 蛋白过表达与细胞增殖失控、凋亡抑制关系密切,在胶质瘤恶性进展中起重要作用。     

野生型p53基因诱导凋亡相关基因ANNEXIN A2的表达研究

目的探讨胡基因过表达介导不同转移潜能肿瘤细胞的凋亡分子机理，寻找与细胞凋亡和肿瘤转移的相关基因。方法应用mRNA差异显示方法分析腺病毒介导的野生型,053基因感染不同转移潜能的肺癌细胞系前后存在的表达差异基因，并用逆转录一聚合酶链反应、Northern印迹和Western印迹方法加以验证。结果分析发现，在柳基因诱导后ANNEXIN A2基因的表达显著差异有统计学意义，经加基因诱导后ANNEXIN A2基因的表达有明显下调。并且以Arfip 973细胞的表达缺失最为显著。经逆转录一聚合酶链反应、Northern印迹和Western印迹方法也验证了这种差异的存在。结论表明ANNEXIN A2基因的表达与p53基因诱导的肿瘤细胞凋亡存在密切的相关性。     

p53、c-erbB-2癌基因蛋白表达与胃癌生物学行为的关系

目的：探讨ｐ５３、ｃ－ｅｒｂＢ－２表达与胃癌生物学行为的关系。方法：利用微波免疫组化方法研究７０例胃癌及２０例胃癌前病变ｐ５３、ｃ－ｅｒｂＢ－２蛋白的表达。结果：正常胃粘膜和肠化生上皮ｐ５３及ｃ－ｅｒｂＢ－２均阴性，中、重度异型增生及胃癌组织中ｐ５３阳性率分别为１５．０％和５１．４％。ｃ－ｅｒｂＢ－２阳性率分别为１０．０％和４０．０％。ｐ５３与胃癌组织学类型、组织发生及分化程度等有关（Ｐ＜０．０５），而ｃ－ｅｒｂＢ－２则与胃癌分化程度、胃癌浸润深度等有关（Ｐ＜０．０５）。在低分化腺癌癌巢边缘部，硬癌内呈浸润性生长的细胞以及脉管内转移性癌栓等处，除了癌细胞核内ｐ５３表达较强外，胞浆也呈弥漫性染色，表明胞浆阳性的癌细胞具有更强的侵袭性。在非浸润进展组或随患者生存期的延长，胃癌组织内ｐ５３及ｃ－ｅｒｂＢ－２的阳性率有下降的趋向。结论：ｐ５３可作为临床筛选胃癌、癌前期病变以及进行早期诊断的有用指标，ｐ５３与ｃ－ｅｒｂＢ－２一起可用于判断胃癌预后，监测病情     

食管癌变过程中p53、c-myc、bcl-2表达及其与细胞凋亡的关系

目的：探讨食管癌变过程中肿瘤抑制基因ｐ５３和癌基因ｃ－ｍｙｃ、ｂｃｌ－２的变化及其与细胞凋亡的关系。方法：采用免疫组化法（ＡＢＣ）检测２７９例食管粘膜活检组织中ｐ５３、ｃ－ｍｙｃ、ｂｃｌ－２的表达以及细胞凋亡的变化。结果：从食管正常上皮到基底细胞增生、间变和癌，ｐ５３、ｃ－ｍｙｃ、ｂｃｌ－２免疫阳性表达率及细胞凋亡发生率和细胞凋亡指数（ＡＩ）均呈升高趋势，而且在同一阶段病变，ｐ５３和ｃ－ｍｙｃ阳性表达时凋亡指数高于其阴性表达，而ｂｃｌ－２阳性表达时凋亡指数低于其阴性表达。结论：在食管癌变过程中可能有多种肿瘤抑制基因和癌基因参与，细胞凋亡在食管癌变过程中可能有重要的生物学意义。     

ASPP2对p53家族成员诱导凋亡功能的调控作用及其在肿瘤治疗中的意义

ASPP2（p53凋亡激活蛋白2，Apoptosis Stimulating Proteins of p53 2）作为p53家族共同转录激活辅因子能和p53野生型、p63和p73结合，并促进其对下游促凋亡靶基因的转录，促进细胞凋亡。研究表明ASPP2参与细胞生长，凋亡以及损伤应激等一系列的生理反应，对研究肿瘤发生和治疗具有重要意义。     

胃肠道间质瘤中p53和bcl-2表达与预后的关系

目的探讨细胞凋亡相关基因p53和bc l-2在胃肠道间质瘤(gastrointestinal strom al tumors,G ISTs)中的表达与预后关系。方法对194例G ISTs构建组织微阵列(TMA),采用免疫组化EnV ision法检测G ISTs组织中p53和bc l-2基因蛋白的表达。结果在p53 TMA中,184例可评估(94.8%),在bc l-2 TMA中181例可评估(93.3%)。p53和bc l-2基因蛋白阳性率分别为34.8%和59.1%。p53蛋白阳性表达率与肿瘤大小、NIH分级、肿瘤部位、坏死、细胞密集程度、核分裂象和转移复发有关。bc l-2阳性表达率与肿瘤大小、NIH分级、肿瘤部位、坏死和黏膜受累及有关。p53蛋白阳性和阴性表达者的5年生存率分别为40.1%和76.5%,两者比较差异有显著性(P<0.01)。bc l-2阳性和阴性表达者的5年生存率分别为55.1%和76.2%,两者比较差异有显著性(P<0.05)。p53蛋白阳性组和阴性组与bc l-2蛋白的阳性表达差异有显著性(P<0.01)。结论p53、bc l-2表达与G ISTs预后有关,p53、bc l-2可作为判断G ISTs预后的标志物。     

Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer

Cancer cells show a higher rate of anaerobic respiration than normal cells. The exact mechanisms for this higher glycolysis rate in cancer cells remain to be elucidated. The results of recent studies have indicated that p53, the most commonly mutated tumor suppressor gene, may have important functions in the regulation of energy-generating metabolic pathways that switch from oxidative phosphorylation to glycolysis via the synthesis of cytochrome c oxidase 2 (SCO2), p53-transactivated TP53-induced glycolysis (TIGAR), and apoptosis regulator. We evaluated the expression of p53, SCO2, TIGAR, and COX in 113 cases of invasive breast cancer using immunohistochemistry. A high expression of p53, SCO2, TIGAR, and COX was noted in 27.5% (31 cases), 84.1% (95 cases), 74.3% (84 cases), and 73.4% (83 cases) of the breast tumors, respectively. A high p53 expression was significantly associated with low expression levels of SCO2 (P = .008), COX (P < .0001), and TIGAR (P = .007). On the survival analysis, the low SCO2-expressing breast cancer patients showed a significantly poorer prognosis than that of the high SCO2-expressing breast cancer patients (P = .0078). These results suggest that p53 can modulate the metabolic pathways via the proteins SCO2 and TIGAR in human breast cancer.     

胃复康对人SGC-7901胃癌细胞株p53、bcl-2基因表达的影响

目的探讨中药胃复康对人SGC-7901胃癌细胞株p53、bcl-2基因表达的影响。方法PRMI1640血清培养的人SGC-7901胃癌细胞株分为胃复康实验组、生理盐水对照组和顺铂(DDP)化疗组。利用血清药理学方法制备药物血清,作用48h后,应用免疫细胞化学方法和图像分析方法观察胃复康、DDP对人SGC-7901胃癌细胞株p53、bcl-2基因表达影响。结果免疫细胞化学法显示抑癌基因p53和癌基因bcl-2主要定位在细胞质内。胃复康、DDP药物血清作用后,p53表达明显增强,bcl-2表达明显降低;随着作用时间延长,两种基因表达改变更明显。胃复康、DDP药物血清组p53和bcl-2表达的光密度值(AOD)与对照组差异显著(P<0.01)。结论中药胃复康药物血清上调p53和下调bcl-2的表达可能是其抑制胃癌细胞株SGC-7901的作用机制之一。     

清络通痹颗粒对胶原性关节炎大鼠滑膜细胞凋亡相关基因p53和bcl-2表达的影响

目的：观察清络通痹颗粒对胶原性关节炎大鼠滑膜凋亡相关基因的影响。方法：采用牛Ⅱ型胶原制备大鼠胶原性关节炎模型，提取滑膜细胞总RNA，采用RT—PCR技术，检测药物对滑膜细胞p53 mRNA、bcl-2 mRNA的影响。结果：胶原性关节炎大鼠滑膜细胞ps3mRNA、bcl-2mRNA表达较正常组明显升高（P〈0．01），清络通痹颗粒7．2g／kg可明显下调胶原性关节炎大鼠滑膜细胞p53 mRNA、bcl-2mRNA的水平（P〈0．05，P〈0．01）。结论：清络通痹颗粒可能通过下调滑膜细胞凋亡相关基因p53 mRNA、bcl-2 mRNA表达，促进滑膜细胞的凋亡而发挥治疗作用。     

c—erbB—2和p53基因表达与胃癌浸润转移的关系

目的：探讨胃癌组织中c-erbB-2和p53基因的表达与胃癌发生和浸润转移的关系。方法：应用荧光原位杂交技术对55例胃癌的常规石蜡标本进行检测,结果：c-erbB-2和p53基因表达的阳性率分别为36．6％和45．45％,其中在肠型和弥漫型胃癌中,c-erbB-2和p53阳性率分别为51．615和16．67％,p53阳性率分别为25．81％和70．83％,两种基因在两型间的差异有显著性意义（P＜0．05）,c-erbB-2和p53基因表达与胃的组织分级有关（分别为P＜0．05及P＜0．01）c-erbB-2和p53基因表达与胃癌的浸润深度有相关性（分别为P＜0．01及＜0．05）,c-erbB-2;基因表达与胃癌的淋巴结内转移有显著性意义（P＜0．05）,结论：c-rebB-2和p53基因有助于确定胃癌的生物学行为。     

No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis

Inactivation of wild-type p53 during gastric carcinogenesis is usually caused by mutations within exons 5–8 of the p53 gene leading to mutated, usually immunohistochemically detectable p53 proteins. However, functional inactivation of wild-type p53, mimicking mutational inactivation, may also result from binding to overexpressed MDM2 protein. While these two mechanisms of p53 inactivation are considered to be mutually exclusive, no data exist as to whether MDM2 overexpression occurs during gastric carcinogenesis. MDM2 protein overexpression was therefore studied in relation to p53 protein accumulation in gastric carcinogenesis. Forty-five paraffin-embedded gastrectomy specimens from early gastric carcinomas were examined for the presence of chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type was reassessed for all early carcinomas. p53 protein accumulation was examined using the monoclonal antibody DO-7. MDM2 protein overexpression was assessed with the monoclonal antibody SMP-14. Complete absence of nuclear p53 protein accumulation was observed in chronic active gastritis, chronic atrophic gastritis, and intestinal metaplasia, irrespective of the subtype. In gastric dysplasia (one mild, two moderate, one severe), only severe dysplasia was p53-positive. Intestinal-type (n=20) and diffuse-type early gastric carcinoma (n=25) were p53-positive in 70 and 52 per cent of the cases, respectively. MDM2 protein overexpression was not observed during gastric carcinogenesis, either in the p53-positive or in the p53-negative cases. In conclusion, it appears that functional inactivation of wild-type p53 by MDM2 protein overexpression plays no role in (early) gastric carcinogenesis. © 1998 John Wiley & Sons, Ltd.     

Bcl-2, iNOS,p53 and PCNA expression in normal,disordered proliferative,hyperplastic and malignant endometrium

We attempted to determine Bcl-2, inducible nitric oxide synthase (iNOS), p53 and proliferating cell nuclear antigen (PCNA) expression, and the relationships between them, in endometrioid adenocarcinomas and precursor lesions. Expression of Bcl-2, iNOS, p53 and PCNA were investigated immunohistochemically in 91 samples from benign (proliferative (pEM), secretory (sEM), disordered proliferative (dEM), inactive/atrophic (aEM), hyperplastic endometrium) and malignant endometrial tissue. Staining scores for Bcl-2 in the dEM, endometrial hyperplasia (EMH) and endometrioid cancer (ECA) groups were higher than in the pEM group (P = 0.004; P = 0.036 and P = 0.020, respectively). A significant difference in proliferating cell nuclear antigen staining was found between simple and complex EMH samples (P = 0.000). An inverse relationship was found between iNOS and p53 in the hyperplasia group (r = -0.533, P = 0.019). While a significant difference was found in p53 staining in ECA between the pEM, dEM and EMH groups, no such difference was found in iNOS staining. In addition, there was no direct relationship between iNOS and p53 in the ECA group. It was concluded that the interaction between iNOS, p53 and Bcl-2 in proliferative processes in the development of type 1 endometrioid adenocarcinomas is different from that in tumors originating in other organs.     

Possible Relation of p53 and mdm-2 Oncoprotein Expression in Thyroid Carcinoma: A Molecular-Pathological and Immunohistochemical Study on Paraffin-Embedded Tissue

Routinely processed tissues from a series of benign and malignant thyroid lesions were immunohistochemically investigated with antibodies against p53 and mdm-2. p53 was immunolocalized in <10% of nuclei in 2/80 nodular goiters, 2/60 follicular adenomas, 26/68 follicular carcinomas, 7/40 papillary carcinomas, 3/10 “insular” carcinomas, and 10/31 anaplastic carcinomas. More than 10% positively stained nuclei were found in 2 widely invasive follicular, 2 insular, and 15 anaplastic carcinomas. All p53-positive cases showed a concomitant immunohistochemical mdm-2 expression; an immunohistochemical colocalization on serial section was demonstrated in 12 anaplastic carcinomas. Screening by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis of these 12 cases revealed no relevant mutations in the coding regions of exons 2–11 of the p53 gene. Additionally, 1 follicular adenoma, 6 follicular carcinomas (4 minimally and 2 widely invasive), 1 papillary, and 2 poorly differentiated insular carcinomas were mdm-2 positive without immunohistochemically detectable p53 expression. These results provide evidence that wild-type p53 expression in thyroid carcinomas may be associated with mdm-2 induced formation of stable complexes. However, the role of p53 mutations and p53 protein inactivation owing to other factors (e.g., mdm-2) in the progression of thyroid carcinomas is still poorly understood.     

p53 but not bcl-2 is expressed by most cholangiocarcinomas: a study of 28 cases

AIMS: To examine the frequency and pattern of expression of p53 and bcl-2 in archival material from patients with cholangiocarcinomas and to evaluate their respective roles in its pathogenesis, diagnosis and prognosis. METHODS AND RESULTS: Twenty-eight surgical cases of cholangiocarcinomas diagnosed at St James's University Hospital and 16 control cases were immunostained with monoclonal antibodies to p53 and bcl-2 using streptavidin-biotin complex method. Pressure cooker was used for antigen retrieval. Of the cholangiocarcinomas, 85.7% (24/28) overexpressed p53. The intensity of staining in these cases varied from 1+ in 2, 2+ in 10 and 3+ in 12 cases. None of the 28 tumours expressed bcl-2. The well differentiated nature of the tumour made assessment of dysplasia difficult, however, where present it did not express p53 or bcl-2. The bile duct epithelium adjacent to the tumour and in the control cases did not show any significant nuclear staining for either antigen. CONCLUSIONS: Overexpression of p53 appears to play an important role as a late event in the pathogenesis of cholangiocarcinomas, while we found no evidence of bcl-2 overexpression. The expression of p53 in 86% of the invasive tumours, as compared to its lack in the adjacent normal bile duct epithelium, makes it potentially useful in the diagnostic histopathology of these cases.