PCNA,p53蛋白在肝癌临床中的意义

原发性肝癌易发生肝内转移，其术后复发率很高，为寻找有效的方法以降低术后的复发率，我们用抗ｐ５３和ＰＣＮＡ单克隆抗体对１０２例手术切除的肝癌标本作免疫组化检测。本文分析了肝癌的不同病理形态，ｐ５３，ＰＣＮＡ情况，结果表明：ＰＣＮＡ指数与ｐ５３的表达呈正相关系，ＰＣＮＡ指数与肿瘤大小，肿瘤包膜，组织分化程度无统计学差异；ｐ５３的表达多见于大肝癌中，但与肿瘤包膜，组织分化程度无统计学差异。ＰＣＮＡ和ｐ５     

人肝细胞癌及癌旁组织中p53蛋白和PCNA的表达

应用免疫组化方法检测了７３例肝细胞癌及癌旁组织中ｐ５３蛋白的表达，７０例肝细胞癌及癌旁组织中ＰＣＮＡ的表达。结果ｐ５３蛋白、ＰＣＮＡ在肝细胞癌中阳性表达率显著高于癌旁组织，且与肝细胞癌分化程度密切相关。癌旁组织中，ｐ５３蛋白表达仅见于增生结节中，肝硬化组织均为阴性；增生结节中ＰＣＮＡ阳性表达显著高于肝硬化组织。提示ｐ５３基因突变是肝细胞癌的频发事件，在肝细胞癌的发生发展中起重要作用；增生结节细胞的增殖活性增强，是肝细胞癌的癌前病变。作者还讨论了ｐ５３蛋白和ＰＣＮＡ表达间的关系     

胃癌组织中p16、p53、Rb和增殖细胞核抗原的表达与临床病理特征的关系

目的：研究胃癌中ｐ１６、ｐ５３、Ｒｂ蛋白及ＰＣＮＡ表达与临床病理的关系。方法：应用免疫组化ＳＰ法对６３例胃癌组织中ｐ１６、ｐ５３、Ｒｂ和ＰＣＮＡ进行检测。结果：６３例胃癌组织中ｐ１６、ｐ５３、Ｒｂ和ＰＣＮＡ进行检测。结果：６３例胃癌组织中ｐ１６、ｐ５３、Ｒｂ蛋白和ＰＣＮＡ表达阳性率分别为６３．５％、６０．３％、６５．６％和７１．４％。ｐ１６蛋白阳性表达随着肿瘤分化程序降低、恶性程度增加和浸润深度的     

大肠癌组织p53、PCNA表达与临床病理及预后的关系

目的：探讨突变型ｐ５３ 蛋白、增殖细胞核抗原（ＰＣＮＡ） 在结直肠癌细胞中的表达情况与临床病理及预后的关系。方法：用ＬＳＡＢ 免疫组化方法检测１７２ 例癌组织中的ｐ５３ 蛋白、ＰＣＮＡ 的表达情况,用Ｌｏｇｉｓｔｉｃ 回归分析ｐ５３ 表达的相关因素,Ｃｏｘ 模型分析ｐ５３ 、ＰＣＮＡ 表达对预后的的影响。结果：ｐ５３ 、ＰＣＮＡ 阳性率分别为４３－６ ％ （７５／１７２） 、９１－３ ％ （１５７／１７２） 。ｐ５３ 表达与临床病理因素无关,ｐ５３ 阳性预后比阴性差,ｐ５３ 阳性常伴有ＰＣＮＡ 过度表达,但ＰＣＮＡ 高表达,预后有好的趋势。结论：结直肠癌ｐ５３ 突变的癌细胞多呈高增殖状态,ｐ５３ 阳性、ＰＣＮＡ 中、低强度表达是预后差的生物学指标。ＰＣＮＡ 高表达,是癌细胞处于高增殖状态、对化疗敏感的标志,对该类病人给予辅助化疗可望提高根治术疗效。     

骨肉瘤组织中p53蛋白表达与PCNA的相关性研究

目的 研究骨肉瘤组织中ｐ５３蛋白表达与ＰＣＮＡ的相关性。方法 应用免疫组化方法测定３３例骨肉瘤中ｐ５３基因、ＰＣＮＡ的表达,均行手术治疗,１９例获得平均１年７个月的随访,１１例发生肺转移（６例死亡）３例术后复发。结果 ｐ５３阳性表达率为５７．６％,预后良好组ｐ５３阳性表达率明显低于预后不良组;ＰＣＮＡ阳性表达率为６６．７％。结论 ｐ５３蛋白阳性表达的骨肉瘤有较强的增殖能力。     

X—刀治疗后脑胶质瘤中PCNA和p53基因表达的变化及意义

为了探讨经Ｘ－刀治疗后脑胶质瘤中ＰＣＮＡ和ｐ５３基因表达的变化，作者采用组织免疫组化ＡＢＣ法，检测３６例经Ｘ－刀治疗后脑胶质瘤和３０例对照组的标本，分别计算增殖细胞核抗原标记率（ＰＣＮＡ－ＬＩ）和ｐ５３基因表达标记率（ｐ５３－ＬＩ）。结果表明，治疗组的ＰＣＮＡ－ＬＩ明显低于对照组（Ｐ＜０．０５），治疗组的ｐ５３－ＬＩ明显高于对照组（Ｐ＜０．０５）；治疗组和对照组内ＰＣＮＡ与ｐ５３基因的表达均呈显著性正相关关系。作者认为，ＰＣＮＡ和ｐ５３基因的表达可作为脑胶质瘤对放射敏感性和恶性程度的标志之一。     

大肠癌旁粘膜细胞增殖模式与术后复发机制的探讨

目的：探讨大肠癌旁粘膜细胞增殖模式变化与肿瘤术后复发的关系。方法：用免疫组化染色方法对７８例大肠癌标本的癌组织、癌旁粘膜及１２例正常大肠粘膜进行ｐ５３蛋白、增殖细胞核抗原（ＰＣＮＡ）检测,并进行随访。结果：癌组织ＰＣＮＡ高表达明显高于癌旁（Ｐ＜００１）,癌旁ＰＣＮＡ高表达与隐窝增殖区扩大、上移,明显影响术后第１年局部复发死亡率（Ｐ＜００１）,癌组织ｐ５３蛋白阳性表达率６１５４％,癌旁为２６９２％,癌及癌旁ｐ５３阳性表达不影响细胞增殖活性及术后第一年内的复发死亡率（Ｐ＞００５）。结论：大肠癌的复发可能与大肠癌的发生一样是正常隐窝增殖分化失调的顺序过程。ＰＣＮＡ可直观表现其增殖活性及增殖模式。ｐ５３突变及表达是多中心性的,癌旁ｐ５３突变点的存在是肠癌局部复发的潜在因素。     

p53蛋白,PCNA在大肠癌中的表达及临床意义

ｐ５３蛋白、ＰＣＮＡ在大肠癌中的表达及临床意义殷健１梁延杰１汪鸿志关键词大肠肿瘤ｐ５３蛋白ＰＣＮＡ中图号Ｒ７３５．３４本文应用ＬＳＡＢ法对存档的大肠癌组织进行ｐ５３蛋白、ＰＣＮＡ单抗的免疫组化染色观察，并对患者进行生存期随访，旨在探讨大肠癌ｐ５３过度...     

结直肠肿瘤p~（53）蛋白表达与细胞增殖

应用免疫组织化学ＡＢＣ法检测６９例结直肠癌，１１例腺瘤，３０例癌旁粘膜及１５例正常粘膜的Ｐ￣５３蛋白表达及增殖细胞核抗原（ＰＣＮＡ），结果显示：ｐ￣５３蛋白表达的结直肠癌细胞增殖指数高，腺瘤ＰＣＮＡ阳性细胞多集中于细胞增殖区，与ｐ￣５３蛋白阳性表达区相仿；癌旁粘膜增殖指数与严ｐ￣５３表达无关。这表明：ｐ￣５３蛋白表达与结直肠肿瘤细胞增殖及腺瘤恶性转化有关。     

肺癌p53蛋白和增殖细胞核抗原的检测及其意义

目的：探讨ｐ５３蛋白、ＰＣＮＡ联合表达在临床中的意义。方法应用免疫组织化学Ｓ－Ｐ法检测１０１例肺癌中ｐ５３蛋白、ＰＣＮＡ的表达。结果ｐ５３蛋白在肺癌组织中有较高的表达。总阳性率为５９．４％（６０／１０１）。Ｐ５３蛋白表达与肿瘤分化程度呈正相关（Ｐ〈０．０５）。而与肺癌患者的生存期呈负相关（Ｐ〈０．０１）。Ｐ５３蛋白表达与ＰＣＮＡ染色密切相关（Ｐ〈０．０５）。结论Ｐ５３蛋白表达可作为判断肺癌患者预后     

Down-regulation of tumor suppressor gene PTEN, overexpression of p53, plus high proliferating cell nuclear antigen index predict poor patient outcome of hepatocellular carcinoma after resection

We aimed to evaluate the interaction of two tumor suppressor genes PTEN and p53 and their relationship with cell cycle protein proliferating cell nuclear antigen (PCNA) in hepatocellular carcinoma (HCC). A total of 124 resected HCC paraffin specimens were collected from 1987 to 1999 for immunohistochemistry. Expression of PTEN, p53 and PCNA in HCC were analyzed for clinicopathologic correlation. The study revealed decreased or absent PTEN immunostaining (PTEN down-regulation) in 42.7% and positive p53 (p53+) immunostaining in 41.9% of HCC. There was a positive correlation between PTEN down-regulation and p53 (+) (P=0.001). PTEN down-regulation or p53 (+) correlated with increased HCC dedifferentiation, advanced pathologic stages and high PCNA labeling index (LI) of tumors (P<0.05). Patients with either PTEN down-regulation, p53 (+), or high PCNA LI had shorter survival and higher recurrence rates than patients with intact PTEN expression, p53 (-), or low PCNA LI respectively (P<0.05). By combining the three genes, patients with all PTEN down-regulation (+)/p53 (+)/high PCNA LI had the shortest overall survival (P<0.001) and the highest recurrence rates (P<0.001), followed by patients with two, one and none of three events accordingly. Combination of PTEN/p53/PCNA represented an independent prognostic factor for tumor recurrence and disease-specific survival (P<0.05). In conclusion, the down-regulated PTEN expression and p53 over-expression are involved in the pathogenesis of HCC. They correlate with high PCNA expression, HCC de-differentiation and advanced HCC stages. A combination of the three genes predicts patient outcome more powerfully than any of the individual genes.     

Increased proliferative activity caused by loss of p21(WAF1/CIP1) expression and its clinical significance in patients with early-stage gastric carcinoma

BACKGROUND: Recurrences of gastric carcinoma are likely to take on a variety forms, even after patients undergo curative resection for early-stage gastric carcinoma. It is important to identify the biologic markers that predict tumor progression and survival in these patients. Proliferating cell nuclear antigen (PCNA) acts as a processivity factor for DNA polymerase delta, which is involved directly in DNA synthesis, and the PCNA level is correlated with the proliferative state of cells. p21(WAF1/CIP1) interacts with PCNA to inhibit DNA synthesis and plays a central role in regulating the cell cycle. The authors investigated patients with early-stage gastric carcinoma to determine the clinical significance of proliferative activity and p21 expression. METHODS: Tissue specimens from 133 Japanese patients with early-stage gastric carcinoma that invaded the submucosal layer were immunostained with a monoclonal antibody against PCNA and p21(WAF1/CIP1), and the correlations between the PCNA labeling index and p21(WAF1/CIP1) expression as well as clinicopathologic factors were investigated. RESULTS: The PCNA labeling index varied from 9.9% to 81.4%, (mean, 31.2%). The incidence of p21 positive expression was 87 of 133 patients (65.4%). The patients with a high labeling index had a significantly higher rate of lymph node metastasis (P < 0.01) and loss of p21(WAF1/CIP1) expression (P < 0.05) compared with the patients with a low labeling index. The 5-year survival rate for patients in the high labeling index group (87.0%) was significantly lower compared with the 5-year survival rate for the patients in the low labeling index group (98.6%; P < 0.05). CONCLUSIONS: Loss of p21(WAF1/CIP1) expression contributes to the amplification of proliferative activity in patients with early-stage gastric carcinoma. Estimation of the proliferative activity of early-stage gastric carcinoma provides information on lymph node metastasis and prognosis. Even after patients undergo curative resection, those with early-stage gastric carcinoma should be followed closely.     

50例新疆维吾尔族食管鳞癌组织中survivin、p53蛋白的表达及临床意义

目的:探讨survivin、p53蛋白在维吾尔族食管鳞癌组织中的表达及其与临床病理指标的相关性,并进一步探讨其在食管鳞癌发生、发展中的作用.方法:应用免疫组织化学法(EnVision二步法),检测survivin和p53蛋白在50例食管鳞癌组织及18例食管正常切缘组织中的表达情况.结果:50例食管鳞癌中survivin和p53基因的阳性表达率为66％和38％,明显高于对照组(食管正常切缘组织)(P＜0.05).survivin、p53蛋白在中晚期食管癌中的阳性表达与食管癌的分期、分化程度相关(P＜0.05),而与食管鳞癌患者的年龄、性别、肿瘤大小、浸润深度、有无淋巴结转移无关(P＞0.05).survivin与p53蛋白在食管鳞癌中的表达无显著相关(r =0.040,P＞0.05).结论:survivin、p53蛋白在食管鳞癌组织中的表达明显高于食管正常组织.表达的高低与食管鳞癌临床分期、病理分化程度有关,有助于判断食管鳞癌的恶性程度及临床预后.     

PCNA表达与脑胶质瘤复发的相关性分析

目的探讨增殖细胞核抗原（proliferation cell nuckearantigen,PCNA）表达在胶质瘤术后复发中的意义。方法通过对焦作市人民医院神经外科2002年1月～2007年12月手术后病理检查证实为胶质瘤的53例患者的电话复访、信件回访及门诊复诊的回访,以复查头颅CT或头颅MRI为标准,择出来见复发组32例,复发组21例,对其病理组织采用链霉菌抗生物素蛋白-过氧化物酶连接法（即S—P法）进行PCNA的测定,观察PCNA在不同组别中的表达差异。结果复发组PCNA阳性表达率是71．43％（15／21）,未复发组是21．88％（7／32）,两组间有明显差异（P〈0．05）。结论PCNA表达可作为预测脑胶质瘤是否复发的参考因素。     

喉癌切缘组织中p53 p21及PCNA表达及其与肿瘤复发的关系

目的:研究早期喉癌手术切缘阴性组织中p53、p21及PCNA表达的相关性及其与肿瘤复发的关系。方法:选取唐山市协和医院2004年1月至2010年12月间92例早期喉癌患者为研究对象,采用免疫组织化学法联合检测肿瘤及其切缘组织中p53、p21及PCNA的表达情况。电话随访2年以上,对患者生存及肿瘤复发情况进行观察。结果:p53、p21及PCNA蛋白在喉癌组织中的表达与肿瘤的分级及分期无关。92例喉癌患者术后2年内有16例出现复发,复发率为17.39%。喉癌阴性切缘复发和未复发标本中p53、p21及PCNA蛋白表达阳性的切缘复发率分别为50.00%、34.21%和33.33%,明显高于p53、p21及PCNA蛋白表达阴性的切缘（8.33%、5.56%和9.68%）。经统计学分析,喉癌复发标本3种蛋白切缘阳性率明显高于未复发标本,均有显著性差异（P＜0.01）。此外,喉癌阴性切缘组织中p53与p21蛋白的表达有明显的相关性,PCNA的表达与p21的表达亦有明显的相关性。结论:早期喉癌手术病理阴性切缘组织中的p53、p21及PCNA是患者预后的重要生物学标志,联合检测喉癌切缘组织中p53、p21及PC? NA的表达有望作为预测喉癌复发的指标。      

Prognostic significance of Ki-67 (MIB1), PCNA and p53 in cancer of the oropharynx and oral cavity

Up to now results concerning the prognostic value of tumor proliferation markers in squamous cell head and neck carcinoma have been equivocal. Beside biological reasons, different treatment modalities are hypothetically responsible for contradictory findings. The aim of this study was to investigate the relationship between proliferative capacity, represented by the immunohistochemical labeling index of proliferation markers Ki-67, PCNA and p53 status, and treatment failure in a matched-pair study design of recurrent and non-recurrent carcinoma initially treated with primary surgery combined with curative post-operative radiation. From a group of 239 patients with T1–T3 carcinoma of the oropharynx or oral cavity, 28 patients with recurrent disease were selected and matched with 28 patients with non-recurrent disease regarding stage and location of tumor as well as age and therapy. All patients received primary surgery combined with post-operative radiation. Immunohistochemistry determined the p53 status and the PCNA and MIB1 (Ki-67) labeling index. The Ki-67 labeling index was significantly (p=0.032) higher in tumors from patients suffering from treatment failure (mean=59.1%) than in non-failures (mean=50.5%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (53.7%) of the general study population showed a mean time to relapse of 45 months (n=25), whereas mean time-to-relapse was 61.7 months for those cases (n=31) below the median of the general study population (p=0.029). The PCNA labeling index did not correlate significantly with tumor recurrence (mean=50.2% for treatment failures, 45% for non-failures, p=0.31), nor with time-to-relapse (p=0.26). Forty-six percent of tumors showed p53 over-expression. However, there was no significant correlation between p53 over-expression and tumor recurrence or time-to-relapse. We present the largest series of oropharyngeal and oral cavity carcinoma investigated by immunohistochemistry in a controlled study. We conclude that a high Ki-67 labeling index is an indicator for treatment failure in these patients. Like other investigations for different head and neck subsites, we found no relationship between p53 or PCNA status and tumor prognosis. Our data, obtained from a group of patients treated with a combination of surgery and post-operative irradiation, show that for squamous cell carcinoma of the oropharynx and oral cavity the detection of Ki-67 is an unfavorable prognostic factor.     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义(英文)

目的探讨膀胱癌中 bcl-2、p53、PCNA 表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法 SABC 免疫组化分折62例(T1G1-G339例,T2-T4aG3 NOM023例)甲醛固定和石蜡包埋的膀胱癌标本 bcl-2、p53和 PCNA 蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中 PCNA 阳性细胞百分比。TUNEL 法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果 62例膀胱癌中,50例(80.0%)发生 p53突变,与 G1(72.7%)和 G2(78.5%)相比较 G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较 pTa-1期(74.3%)高(P<0.01)。14例(22.5%)发现有 bcl-2表达,bcl-2表达阳性率 G3明显高于 G1和 G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与 p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI 为1.9%～3.5%(平均为2.9%)。统计分析显示 PI 与肿瘤分级、分期关系密切,AI 与肿瘤的分级有明显关系。结论结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中 p53和 PCNA 过表达可能能提供有价值的预后信息。随着肿瘤的进展,肿瘤细胞过度增殖可能伴有频繁的凋亡,但增殖指数的增加明显强于凋亡指数的增加。     

p53蛋白在子宫颈癌组织中表达的临床意义

目的 :探讨 p5 3蛋白在子宫颈癌组织中表达的临床意义。方法 :用鼠抗人 p5 3单克隆抗体 ,以 SP免疫组化法检测 p5 3蛋白。结果 :p5 3蛋白阳性表达率为 5 6 .3 % ,其表达与肿瘤大小、TNM分期、有无淋巴结转移无关 (P>0 .0 5 ) ,与肿瘤分化程度有关 (P<0 .0 1)。 p5 3蛋白阳性与阴性组比较 ,其术后生存率差异有显著性 (P<0 .0 1)。结论 :子宫颈癌组织中 p5 3蛋白表达与肿瘤大小、TNM分期及有无淋巴结转移无关 ,与肿瘤分化程度密切相关 ,并可用于判断预后。     

涎腺癌中增殖细胞核抗原的表达及意义

目的探讨增殖细胞核抗原(proliferating cell nuclear antigen PCNA)在涎腺癌中的表达及临床病理学意义.方法采用免疫组化S-P法检测62例涎腺癌(10例恶性混合瘤;20例腺样囊性癌;32例粘液表皮样癌)中PCNA表达情况.结果PCNA在不同类型的涎腺癌中表现出不同的表达水平及分布特征,PCNA阳性程度与肿瘤的组织学分级及临床行为(复发、转移)明显相关.结论涎腺癌中PCNA表达水平与细胞分化有关;PCNA指数可作为粘液表皮样癌病理分级的重要参数;PCNA高表达可能是涎腺癌预后不良的标志.     

食管癌组织中p53蛋白表达的临床意义

目的 :探讨p53蛋白表达在食管癌中的临床意义。方法 :用鼠抗人p53单克隆抗体 ,以SP免疫组化法检测p53蛋白。结果 :p53蛋白阳性表达率为 56 3% ,其表达与肿瘤大小、TNM分期、有无淋巴结转移无关 (P >0 0 5) ,与肿瘤分化程度有关 (P <0 0 1)。p53蛋白阳性组与阴性组比较 ,其术后生存率有显著差异 (P <0 0 1)。结论 :食管癌组织中p53蛋白表达与肿瘤大小、TNM分期及有无淋巴结转移无关 ,与肿瘤分化程度密切相关 ,并可用于判断预后