食管癌前病变及原位癌组织中Ki67、p53、iNOS的异常表达

目的研究食管癌高发区癌前病变及癌活检组织标本中Ki67、p53蛋白的异常表达,探讨其与食管癌变的关系及作为早期癌变生物学标志物的可能性。方法对来自食管癌高发区河北磁县的正常食管黏膜组织和轻度、中度、重度不典型增生上皮以及原位癌活检组织共366例,应用免疫组化技术对食管癌变过程中Ki67、p53蛋白的异常表达进行研究。结果在正常黏膜、轻度、中度、重度不典型增生及原位癌组织中,Ki67异常表达检出率分别为0(0/25)、40.5%(30/74)、61.3%(65/106)、76.5%(39/51)和90.0%(72/80),其中异常表达程度在中度以上者分别占0(0/25)、2.7%(2/74)、11.2%(12/106)、41.2%(21/51)和58.8%(47/80);p53蛋白异常表达的阳性率分别为4%(1/25)、39.1%(27/69)、57.5%(61/106)、52.9%(27/51)和67.9%(53/78),其中异常表达程度在中度以上者分别占0(0/25)、10.1%(7/69)、24.5%(26/106)、39.2%(20/51)和48.7%(38/78)。p53蛋白及Ki67在正常黏膜中的表达,与不典型增生总体及原位癌组织的差异均有显著性(P＜0.001)。等级相关分析结果显示,p53、Ki67表达异常与组织学分级均显著相关（相关系数r分别为0.3597和0.5837,P值均＜0.001),而且p53蛋白与Ki67表达之间也具有显著相关性（r=0.5432,P＜0.001）。结论Ki67、p53蛋白异常表达与食管癌癌变过程显著相关,p53基因表达异常及细胞增殖异常与食管上皮的早期癌变有关。p53及Ki67表达改变的时相分布,有可能成为在食管癌前人群中确立高危个体和选择重点化学预防个体的分子生物学标记。p53改变可促使上皮细胞增殖。     

胃癌发生过程中端粒酶活性测定及临床意义

目的：通过检测胃癌及癌前病变组织中端粒酶活性，探讨其在胃癌发生发展中的作用及临床意义。方法：采用SP免疫组化法检测40例胃癌和18例癌前病变（其中慢性萎缩性胃炎伴肠化生10例，非典型增生8例）端粒酶活性。结果：胃癌及癌前病变中端粒酶阳性率分别为92．5％（37／40）和33．3％（6／18），两者比较差异有统计学意义，P〈0．05。端粒酶激活与胃癌的分化程度、病理分期和淋巴结转移无明显相关性，P〉0．05。结论：端粒酶活性表达与胃癌的发生密切相关，利用免疫组化检测端粒酶活性可作为胃癌早期诊断的参考指标，并应对阳性病例进行跟踪随访。     

p14^ARF和p53在子宫内膜癌组织中的表达及其临床意义

目的：研究子宫内膜癌组织中p14^ARE。和p53的表达及意义。方法：采用免疫组化LSAB法，检测118例子宫内膜癌及30例正常宫内膜组织中p14^ARE及p53的表达。结果：p14^ARE。阴性、弱阳性、中度阳性和强阳性表达率在子宫内膜癌中分别为25．4％（30／118）、38．1％（45/118）、14．4％（17／118）和22．0％（26／118），与正常内膜0（0／30）、56．7％（17／30）、33．3％（10／30）和10．0％（3／30）相比差异有统计学意义，P〈0．001，子宫内膜癌中p14^ARE。表达缺失的比例高于正常宫内膜；p14^ARE表达水平与手术病理分期、宫颈间质受累和淋巴结转移相关；与病理分级、组织学类型和肌层侵犯深度无关；不同p14^ARE表达水平患者生存率差异无统计学意义，P=0．5781。p53阴性、弱阳性、中度阳性和强阳性表达率在子宫内膜癌中分别为13．6％（16／118）、40．1％（48／118）、28．0％（33／118）和17．8％（21／118）；与正常内膜相比分别为36．7％（11／30）、36．7％（11／30）、16．2％（5／30）和10．0％（3／30）差异有统计学意义，P=0．01．子宫内膜癌中p53阳性表达的比例高于正常宫内膜；p53表达与肿瘤分期、盆腔淋巴结转移和肌层侵犯深度相关，与病理分级、组织学类型和宫颈间质受累无关；不同p53表达水平患者生存率差异无统计学意义，P=0．4166；在子宫内膜癌组织中p14^ARE。与p53表达呈负相关，r=-0．243，P=0．008。结论：p14^ARE和p53异常表达与子宫内膜癌发生密切相关，但对其预后的影响有待进一步的研究。     

细胞周期调节蛋白在食管癌前病变组织的表达及意义

目的探讨食管癌高发区河南林州市和辉县市内镜活检组织p53、p21、Rb、p16、E2F1和cyclin E的表达变化特征及其与各级病变的关系.方法采用免疫组化卵白素-生物素-过氧化物酶复合物(ABC)方法,分析食管癌高发区食管内镜活检组织p53、p21、Rb、p16、E2F1和cyclin E的表达.结果林州市医院食管内镜活检组织共134例,其中21例食管上皮正常(NOR),45例基底细胞过度增生(BCH),23例间变(DYS),45例原位癌组织(CIS).从NOR→BCH→DYS→CIS,p53和cyclin E的免疫阳性率逐渐增高(P<0.05),分别为23.8%(5/21)、 33.3%(15/45)、56.5%(13/23)和71.1%(32/45);28.6%(6/21)、33.3%(15/45)、56.5%(13/23)和75.6%(34/45);而p21的表达逐渐降低(P<0.05),免疫阳性率分别为71.4%(13/21)、57.8%(26/45)、56.5%(13/23)和 37.8%(17/45).辉县市医院食管内镜活检组织132例,其中NOR 12例,BCH 71例,DYS 27例,CIS 22例.从NOR→BCH→DYS→CIS,Rb和E2F1的免疫阳性率逐渐增高(P<0.05),分别为41.7%(5/12)、62.0%(44/71)、 77.8%(21/27)和90.9%(20/22);50.0%(6/12)、45.0%(32/71)、66.7%(18/27)和68.2%(15/22).而p16的表达逐渐降低(P<0.05),免疫阳性率分别为75.0%(9/12)、73.2%(52/71)、59.3%(16/27)和22.7%(5/22).结论 p53、p21、Rb、p16、E2F1和cyclin E是食管癌变早期重要分子改变,p53、Rb、E2F1和cyclin E的高表达和p21、p16的低表达可能是导致病变持续向癌变方向发生和发展的机制之一.     

survivin和p53在食管鳞癌中的表达及意义

目的探讨凋亡抑制因子survivin和p53在食管鳞癌(ESC)组织中的表达及其与临床病理因素之间的关系.方法应用免疫组织化学S-P法和PowerVisionTM-9000(PV-9000)法检测60例ESC、15例食管良性肿瘤和10例癌旁正常食管黏膜组织中survivin和p53的表达.结果 60例ESC中survivin和p53的阳性表达率分别为71.7%和65.0%,与食管良性肿瘤(13.3%,0)和癌旁食管正常黏膜组织(0,0)比较,差异均有显著性(P<0.001).survivin和p53的表达强度与ESC的分化程度、临床分期和淋巴结转移均相关(P<0.05),而与肿瘤长度及部位均无相关(P>0.05).survivin与p53的表达呈显著相关(P<0.01).结论 survivin和p53均与ESC的发生发展有关,二者在ESC的发展过程中可能起协同作用.联合检测survivin和p53在ESC中的表达水平,对判定其恶性程度及预后可能具有重要参考价值.     

p14ARF和p53在子宫内膜癌组织中的表达及其临床意义

目的研究子宫内膜癌组织中p14ARF和p53的表达及意义.方法采用免疫组化LSAB法,检测118例子宫内膜癌及30例正常宫内膜组织中p14ARF及p53的表达.结果p14ARF阴性、弱阳性、中度阳性和强阳性表达率在子宫内膜癌中分别为25.4%(30/118)、38.1%(45/118)、14.4%(17/118)和22.0%(26/118),与正常内膜0(0/30)、56.7%(17/30)、33.3%(10/30)和10.0%(3/30)相比差异有统计学意义,P<0.001,子宫内膜癌中p14ARF表达缺失的比例高于正常宫内膜;p14ARF表达水平与手术病理分期、宫颈间质受累和淋巴结转移相关;与病理分级、组织学类型和肌层侵犯深度无关;不同p14ARF表达水平患者生存率差异无统计学意义,P=0.578 1.p53阴性、弱阳性、中度阳性和强阳性表达率在子宫内膜癌中分别为13.6%(16/118)、40.1%(48/118)、28.0%(33/118)和17.8%(21/118);与正常内膜相比分别为36.7%(11/30)、36.7%(11/30)、16.2%(5/30)和10.0%(3/30)差异有统计学意义,P=0.01,子宫内膜癌中p53阳性表达的比例高于正常宫内膜;p53表达与肿瘤分期、盆腔淋巴结转移和肌层侵犯深度相关,与病理分级、组织学类型和宫颈间质受累无关;不同p53表达水平患者生存率差异无统计学意义,P=0.416 6;在子宫内膜癌组织中p14ARF与p53表达呈负相关,r＝-0.243,P＝0.008.结论p14ARF和p53异常表达与子宫内膜癌发生密切相关,但对其预后的影响有待进一步的研究.     

端粒酶催化亚基和C-myc在大肠癌中的表达

采用免疫组化SP法检测78例大肠癌组织、20例癌旁组织和20例大肠腺瘤中hTERT和C-myc蛋白的表达,并分析其相关性.大肠癌中hTERT和C-myc蛋白表达率最高(P＜0.05);hTERT和C-myc蛋白表达水平与大肠癌的临床分期、分化程度和淋巴结转移密切相关(P＜0.05);hTERT和C-myc蛋白之间存在显著相关性(P＜0.05).     

宫颈脱落细胞p16INK4A和p57KIP2表达及其临床意义的初步探讨

目的：研究p16^INK4A和p57^KIP2在宫颈脱落细胞的表达及其与临床病理指标的关系。方法：采用免疫细胞化学二步法，检测81例不同病变阶段的宫颈脱落细胞标本中p16^INK4A和p57^KIP2的表达。结果：p16^INK4A在ASC—US、低级别上皮内病变（CINⅠ）、高级别上皮内病变（CINⅡ～Ⅲ）和浸润性癌的阳性表达率分别为6．25％（1／16）、58．8％（10／17）、89．2％（33／37）和100．0％（11／11），各组之间的差异有统计学意义，χ^2=38．806，P〈0．001；p57^KIP2在高级别上皮内病变（CINⅡ～Ⅲ）和浸润性癌的阳性表达率为27．1％（13／48），与ASC—US和低级别上皮内病变（CINⅠ）的阳性表达率为69．7％（23／33）比较，差异有统计学意义，χ^2=15．194，P=0．002。结论：p16^INK4A和p57^KIP2在宫颈脱落细胞中的表达与临床病理指标密切相关，p16^INK4A和p57^KIP2可以作为宫颈癌前病变高危人群的筛查指标。     

宫颈脱落细胞p16INK4A和p57KIP2表达及其临床意义的初步探讨

目的:研究p16INK4A和p57KIP2在宫颈脱落细胞的表达及其与临床病理指标的关系。方法:采用免疫细胞化学二步法,检测81例不同病变阶段的宫颈脱落细胞标本中p16INK4A和p57KIP2的表达。结果:p16INK4A在ASC-US、低级别上皮内病变(CINⅠ)、高级别上皮内病变(CINⅡ～Ⅲ)和浸润性癌的阳性表达率分别为6.25%(1/16)、58.8%(10/17)、89.2%(33/37)和100.0%(11/11),各组之间的差异有统计学意义,χ2=38.806,P<0.001;p57KIP2在高级别上皮内病变(CINⅡ～Ⅲ)和浸润性癌的阳性表达率为27.1%(13/48),与ASC-US和低级别上皮内病变(CINⅠ)的阳性表达率为69.7%(23/33)比较,差异有统计学意义,χ2=15.194,P=0.002。结论:p16INK4A和p57KIP2在宫颈脱落细胞中的表达与临床病理指标密切相关,p16INK4A和p57KIP2可以作为宫颈癌前病变高危人群的筛查指标。     

p53 Immunohistochemical expression of Egyptian cervical carcinoma

Data concerning the expression of p53 in cervical carcinoma, one of the leading cause of death in developing countries, are still confusing. This study was designed to identify p53 in Egyptian cervical carcinoma in an attempt to evaluate its prognostic significance. Eleven chronic cervicitis and 38 invasive carcinoma (31 squamous cell carcinoma (sqcc) and 7 adenocarcinoma, ranging from stage IB to IVB), were stained with the monoclonal antibody anti p53, DO7, using the microwave for antigen retrieval. No immunoreactivity was detected in chronic cervicitis, while nuclear p53 reactivity was detected in all carcinoma and in squamous intra-epithelial lesions (SIL) overlying 8 sqcc. P53 immunohistochemical (IHC) expression was more pronounced in early clinical stages (p=0.007) and in adenocarcinoma compared to sqcc (p=0.015). A positive correlation was present between p53 and heat shock protein 70 (hsp70) expressions (p=0.005). No correlation could be found between p53 expression and tumor infiltrating lymphocytes, the presence or absence of either schistosomiasis or HPV infections. It can be concluded, that in the Egyptian population, p53 immunoreactivity appears to be an early event in cervical neoplasm, and seems to play an important role together with other cell regulatory proteins in the process of carcinogenesis, which could be different between sqcc and adenocarcinoma.     

Genomic deletion and p53 inactivation in cervical carcinoma

The tumor-suppressor gene p53 acts as “the guardian of the genome”, sensing DNA damage and initiating protective responses. To examine the hypothesis that p53 abnormality leads to increased genomic alterations in primary tumor cells, our study utilized 51 primary tumors of cervical carcinoma and 10 microsatellite markers. These markers were mapped to the short arms of chromosomes 3 and 5, covering the regions 3p13–25 and 5p15.1–15.3. Genomic deletion on 3p and 5p was correlated with genetic or epigenetic p53 inactivation pathways, including p53 mutation, genetic deletion of p53 and cervical infection with human papillomavirus. The proportion of abnormal p53 was found to be significantly higher in the cases exhibiting loss of heterozygosity (LOH) on 5p (p < 0.001), supporting the hypothesis of the presence of a p53-dependent pathway to cervical tumorigenesis. In contrast, however, LOH on 3p was found to be independent of p53 inactivation. A common deletion region, 3p22–24, was identified in 44% of informative cases, and genomic loss at this specific region was correlated with early tumorigenic onset and poor grade of tumor differentiation. Diversity within the patterns of genomic alteration in the same form of cancer suggests different sets of risk/tumorigenic profiles, molecular pathogenesis, as well as prognosis and outcome. Int. J. Cancer 72:270–276, 1997. © 1997 Wiley-Liss, Inc.     

RAS AND p53 EXPRESSION IN HUMAN THYROID CARCINOMA

Both benign and malignant nodular disorder of the thyroid gland may give rise to similar symptomatology. Even though clinical background and pathologic criteria may predict prognosis, there are still patients without these adverse prognosis indicators who develop subsequent local invasion or distant metastasis after surgical intervention and eventually succumb to the disease.[1] In recent years it has become apparent that malignant transformation is a result of the accumulation of genetic abno…     

p53 expression and prognosis in gastric carcinoma.

Abnormalities of the p53 gene have been identified in many malignancies, with reports of aberration in over half of colorectal, lung, breast and hepatocellular carcinoma cases. The normal gene acts as a recessive oncogene, while mutations change the apparent function to that of a dominant oncogene. In this investigation a 3-layered immunoperoxidase technique was applied to routinely fixed and paraffin-embedded tissue sections from 125 gastric carcinomas, using a polyclonal anti-p53 antibody (CM-I). We found that 57% of these carcinomas expressed high levels of p53 protein (positive nuclear staining). Survival analysis revealed a strong association between p53 status of the tumour and patient survival time after diagnosis (p = 0.02, Mantel-Cox Test); odds ratio of death, 2.09 (95% confidence interval 1.02 to 4.25). The 5-year survival of patients with p53-expressing tumours was 24%, compared with 56% for those non-p53-expressing tumours (the median survival times were 13 and 102 months, respectively).     

p53功能在肝癌中表达的意义

为探讨Ｐ５３功能及某些生物学行为肝癌中表达的意义。方法：收集１９９７年１月至１９９８年１２月５２例原发性肝癌的临床资料，并对这５２例手术切除的肝癌标本，分别用Ｗｅｓｔｅｒｎ ｂｌｏｔ结合ＤＮＡ损伤诱导的方法检测野生型Ｐ５３的功能，免疫组化检测Ｐ５３蛋白的表达，ＰＣＲ／ＳＳＣＰ方法检测Ｐ５３基因在第５－８外显子的丢失情况及免疫组化检测肿瘤增殖细胞核抗原（ＰＣＮＡ）指数。结果：５２例标本中，３１例（５     

CIN和子宫颈鳞癌的HPV16/18感染与p53、MDM2蛋白表达的关系

目的研究子宫颈鳞癌及C IN的HPV感染、p53蛋白和M DM 2蛋白的表达及三者之间的相互关系。方法选取子宫颈鳞癌61例、C IN 47例、正常子宫颈组织54例,分别采用原位杂交技术检测HPV 16/18感染,用免疫组化技术S-P法检测p53蛋白和M DM 2蛋白。结果HPV 16/18感染率鳞癌组为62.3%(38/61),C IN组为70.2%(33/47),对照组为16.7%(9/54)。C IN组和鳞癌组的HPV 16/18的感染率均显著高于对照组(P值均<0.05)。而C IN组与鳞癌组的HPV 16/18感染率差异无显著性(P>0.05)。C IN组、鳞癌组、对照组的p53阳性率分别为19.1%(9/47)、26.2%(16/61)、3.7%(2/54)。C IN组、鳞癌组、对照组的M DM 2阳性率分别为14.9%(7/47)、26.2%(16/61)、7.4%(4/54)。C IN组和鳞癌组的p53阳性率均显著高于对照组(P值均<0.05),C IN组与鳞癌组比较差异无显著性(P>0.05)。M DM 2阳性率鳞癌组显著高于对照组(P<0.05),而在C IN组和鳞癌组之间、C IN组和对照组之间差异均无显著性(P值均>0.05)。在本实验各组中,p53与M DM 2之间的阳性率均无统计学相关(P值均>0.05)。p53阳性率和HPV 16/18感染之间差异无显著性(P值均>0.05),而M DM 2的阳性率与HPV 16/18感染仅在子宫颈鳞癌组呈正相关(P<0.05)。结论C IN及子宫颈鳞癌与HPV 16/18感染关系密切;p53和M DM 2均参与子宫颈癌及癌前病变的发生,但p53的突变、M DM 2的扩增和过表达均不占主导地位。     

p53蛋白表达与HPV16感染相关新疆维吾尔族妇女宫颈癌的关系

目的 探讨p53蛋白表达在HPV16型感染相关的新疆维吾尔族妇女宫颈癌发生发展中的作用。方法 采用半巢式PCR和免疫组化技术检测79例新疆维吾尔族妇女宫颈癌组织中HPV16 DNA和p53蛋白表达情况，探讨其与宫颈癌发生的相关性。结果 在宫颈癌组织中，HPV16检出率为81．0％（64／79），高于对照组7．5％（3／40），二者存在显著性差异（x^2=58．328，P=0．000）。宫颈癌组中p53蛋白阳性率为68.4％（54／79），明显高于正常宫颈组织12．5％（5／40），二者在统计学上有显著性差异（x^2=33．140，P=0．000）。结论 高危型HPV E6介导的p53蛋白降解失活是宫颈癌发生的重要机制之一，但在部分HPV感染的宫颈癌组织中p53蛋白表达蓄积的现象提示宫颈癌的发生还涉及到其它多基因和多步骤的致癌机制。     

p53 expression and p21 expression are mutually exclusive in esophageal squamous cell carcinoma

The accumulation of p53 protein, which is considered to be caused by a p53 gene mutation, is closely associated with poor prognosis in patients with certain types of carcinomas. The progression of esophageal squamous cell carcinoma (ESCC) is also suspected to depend on p53 gene status. We analyzed the relationship between p53 and p21 protein accumulation in ESCC, and simultaneously analyzed the frequency of apoptosis. Formalin-fixed paraffin-embedded sections were taken from 46 patients who underwent esophagectomy for ESCC. These sections were examined by immunostaining with monoclonal antibodies PAb1801 and EA10 to determine p53 and p21 protein accumulation, respectively. We also analyzed the frequency of apoptosis by TdT-mediated dUTP-biotin nick end-labeling (TUNEL). For estimation of the proportion of stained cells, we used computer analysis with NIH image analysis software. p21 protein accumulation showed an almost inverse distribution to that of p53 protein. In areas where both p53 and p21 proteins were accumulated, few apoptotic cells were observed. Particularly in cases of mucosal tumors, p53 protein was prominently accumulated in the lower layer of the tumor, whereas p21 protein accumulation was confined to the upper layer. Our results suggest that progression of esophageal squamous cell carcinoma is controlled by a p53-dependent pathway.     

p21/WAF1, p53 and PCNA expression and p53 mutation status in hepatocellular carcinoma

The cyclin-dependent kinase inhibitor p21/WAF1 is regulated by p53-dependent and p53-independent pathways. In addition, p21/WAF1 binds with proliferating cell nuclear antigen (PCNA) and inhibits the action of PCNA. To investigate the possible role of p21/WAF1 in human hepatocellular carcinomas (HCCs), we examined the expression of p21/WAF1 and its relation with PCNA and p53 expression in 97 surgically resected HCCs by immunohistochemistry and with the mutation status of p53 in 26 HCCs. p53 mutation status was examined by direct DNA sequencing using 3 sets of primers covering exons 5–9. Six of the 26 tumors showed p53 point mutations and only 33% of these HCCs demonstrated p21/WAF1 expression. In contrast, 75% of HCCs without p53 mutations showed p21/WAF1 expression. Of all 97 HCCs, p21/WAF1 expression was significantly higher in the tumors than in corresponding non-tumorous liver. When the tumors were stratified into 2 groups by the median tumor p21/WAF1 score, those with higher expression were found to have a lower incidence of multiple tumor nodules (p = 0.008) and tumor microsatellite formation (p = 0.050). The tumor p21/WAF1 score was positively associated with tumor PCNA expression (p = 0.036) but not with tumor p53 expression. Thus, in HCC, expression of p21/WAF1 is in part dependent on p53 status, but a p53-independent pathway also plays a significant role in the regulation of p21/WAF1 expression. High p21/WAF1 expression is significantly associated with solitary tumor nodules and, to a lesser extent, tumor microsatellites but may not be enough to suppress tumor progression. Int. J. Cancer (Pred. Oncol.) 79:424–428, 1998. © 1998 Wiley-Liss, Inc.