COX-2、PCNA及p53在鼻咽癌中的表达及意义

目的：研究COX-2、PCNA及p53的基因产物在鼻咽癌组织中的表达及与其生物学行为和生存率之间的关系。方法:采用免疫组化SP法检测60例鼻咽癌及30例正常鼻咽组织中COX-2、PCNA 及p53的蛋白表达水平。结果:（1） 鼻咽癌组织COX-2、PCNA 及p53阳性表达率分别为90％、75％和68％ ,明显高于正常鼻咽组织;（2） 鼻咽癌组织COX-2、PCNA及p53的表达与临床分期、分化程度和淋巴结转移相关(P＜0.05);（3） COX-2、PCNA及p53的表达密切相关;（4） 鼻咽癌组织COX-2、PCNA 阳性表达和生存率呈负相关,是鼻咽癌复发的显著预后因素。结论:鼻咽癌组织中COX-2、PCNA表达水平明显上调,与鼻咽癌的发生发展及预后不良有关,免疫组化检测COX-2、PCNA表达可用以判断鼻咽癌患者的预后。     

nm23-H1蛋白和P53蛋白在鼻咽癌的表达

为观察ｎｍ２３－Ｈ１基因产物和Ｐ５３基因产物在鼻咽癌（ＮＰＣ０的表达状态，春一ＮＰＣ的发生及转移、预后的产生。采用Ｓ－Ｐ免疫组织化学方法检测ｎｍ２３－Ｈ１基因产物和Ｐ５３基因产物的表达。结果ｎｍ２３－Ｈ１蛋白的表达率为５０．４％，Ｐ５３蛋白表达率为９０．４％。ｎｍ２３－Ｈ１蛋白在颈部有淋巴结转移包块才的表达率为２７．９％，低于无颈部淋结转移包块者的表达率，两者有非常显著性差异。ｎｍ２３－Ｈ１蛋白及     

Ki-67、p53和VEGF在鼻咽癌组织中的表达及临床意义

目的探讨Ki-67、p53和VEGF在鼻咽癌组织中的表达及其临床意义。方法选择2015年1月至2020年7月在我院初诊的鼻咽癌患者90例为观察组,选择同期50例在我院就诊的鼻咽黏膜慢性炎症患者为对照组。通过免疫组化检测两组鼻咽组织中Ki-67、p53和VEGF的表达,并探讨三个免疫组化指标与临床病理特征之间的关系。结果(1)鼻咽癌组织中Ki-67、p53、VEGF阳性表达均明显高于鼻咽部炎症组(P<0.05)。(2)鼻咽癌组织中Ki-67、p53、VEGF阳性表达与患者的性别、年龄等病理因素没有相关性(P>0.05),与病理分型、颈部淋巴结转移以及临床分期具有密切相关性(P<0.05)。(3)Ki-67、p53、VEGF三者在鼻咽癌组织中的表达相互之间均呈正相关(P<0.05)。结论Ki-67、p53和VEGF与鼻咽癌的发生和发展有密切相关性,三者的检测对鼻咽癌的诊断及治疗具有重要的参考价值。     

Prognostic value of the expression of p53 and bcl-2 in patients with laryngeal carcinoma

Previous studies have yielded inconsistent results on the prognostic significance of p53 and bcl-2 in head and neck cancer. The aim of this study was the evaluation of p53 and bcl-2 protein expression in laryngeal squamous cell carcinoma and to clarify the relationship between them. All patients with laryngeal carcinoma were treated during the period 1991–1993. In the present study, p53 and bcl-2 expression in paraffin sections from 50 cases of laryngeal squamous cell carcinoma were analysed and correlated with routine clinico-pathological parameters. The expressions of p53 and bcl-2 were examined by immunohistochemical staining. Immunoreactivity for p53 was observed in 45 (90%) of carcinomas and bcl-2 immunoreactivity in 7 (14%). No significant correlation between the p53 or bcl-2 expression and patients’ T- or N-stage, histological grading, or overall survival was found. Received: 2 May 2001 / Accepted: 7 June 2001     

Prognostic significance of p53/bcl-2 co-expression in patients with laryngeal squamous cell carcinoma

OBJECTIVE: The p53, bcl-2, and bax genes are known to be involved in control of cell cycle progression and regulation of apoptotic cell death. Although they are frequently altered in laryngeal squamous cell carcinoma, their clinical relevance is not yet fully understood. In the present study, individual and combined expressions of these genes were related with patient survival as well as with proliferative and apoptotic activity. DESIGN: Retrospective study. METHODS: Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. Apoptotic cells were visualized using the nick end labeling method. To assess proliferative activity of tumors, mitotic indices were determined. RESULTS: Age of patients, advanced disease (stages HI and IV), high mitotic activity, positive bcl-2 expression, high level of p53 expression, and p53/bcl-2 co-expression were significantly associated with shortened overall survival in univariate analysis. In multivariate analysis, only age and p53/bcl-2 co-expression had independent prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax ratios, were not associated with patient outcome. A significant positive correlation was found between apoptotic and mitotic activity. However, protein levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of tumor cells. CONCLUSIONS: The co-expression of p53/bcl-2 was an independent predictor of patient outcome and had a prognostic value superior to both parameters considered separately. The rate of apoptosis mainly counterbalanced proliferative activity but appeared not to be significantly influenced by p53, bcl-2, and bax.     

A prospective study of p53 expression and its correlation with clinical response of radiotherapy in nasopharyngeal carcinoma

OBJECTIVES/HYPOTHESIS: Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck that occurs in people in the southeastern Asian area, including Taiwan. The significant association of p53 expression in NPC suggested that p53 overexpression seemed to occur at an early stage in the development of NPC. Alterations of p53 status were probably the most commonly encountered in head and neck carcinomas, and there was extensive evidence that p53 status might determine tumor response to therapy. Ionizing radiation was studied extensively for the relationship between its damaging effect and p53 status in human cancer cells. STUDY DESIGN: This study was carried out to investigate whether there was any correlation between overexpression of p53 protein and locoregional tumor response in patients with NPC treated with 7000 cGy of radiotherapy. METHODS: Sixty-eight patients (50 males, 18 females) with NPC who were diagnosed and treated with radiotherapy were studied prospectively. Before they had received a radiation dose of 7000 cGy in 35 fractions, five fractions a week, p53 status from a nasopharyngeal biopsy was studied using immunohistochemical staining (IHC). RESULTS: The locoregional response rate of primary tumor was analyzed statistically. Forty-seven patients (69.1%) showed positive p53 staining in their tumors. There were 5 positive stains in 6 squamous cell carcinomas (SCC; 83.3%), 34 positive in 53 non-keratinizing carcinomas (NKC; 64.2%), and 8 positive in 9 undifferentiated carcinomas (UC; 88.9%). The mean ages for patients with three different histopathologies were 48.5, 46.1, and 61.1 years. There were 8 patients (7 positive stains, 1 negative stain) with residual tumor after radiotherapy and all were NKC (6 males, 2 females). Therefore, the clinical response rate of primary tumor was 85.1% in positive p53 immunostaining (40 of 47 cases), 95.2% in those with no immunostaining (20 of 21 cases); the former was poorer in locoregional tumor response than the latter, but there was no significant difference (P > .05, chi2 test). CONCLUSIONS: We conclude that there is no statistically significant correlation in locoregional response of primary tumor between p53 overexpression and radiotherapy in patients with NPC (P > .05, Fisher exact test).     

p53、p63、p73在鼻腔鼻窦恶性肿瘤中表达的临床意义

目的:探讨p53、p63、p73在鼻腔鼻窦恶性肿瘤中表达的临床意义及相关性。方法:用免疫组织化学方法检测67例鼻腔鼻窦恶性肿瘤、36例癌旁组织和36例鼻腔鼻窦的非癌组织中p53、p63和p73的表达。结果:p53、p63在鼻腔鼻窦恶性肿瘤中的阳性表达率明显高于癌旁和非癌组织(均P<0.01),p53与p63在鼻腔鼻窦恶性肿瘤中的表达存在正相关(P<0.01);p73在鼻腔鼻窦恶性肿瘤、癌旁和非癌组织中的表达差异无统计学意义(P>0.05)。结论:p53与p63在鼻腔鼻窦恶性肿瘤的发生发展过程中可能存在相关性,是鼻腔鼻窦恶性肿瘤发生过程中的重要因素之一,而p73在鼻腔鼻窦恶性肿瘤的发生过程中可能不发挥作用。     

主要热应激蛋白和p53在鼻咽癌中的表达

目的 :探讨鼻咽癌 (NPC)组织中主要热应激蛋白 (HSPs)和 p5 3表达水平及其临床意义。 方法 :用Westernblot方法检测 38例NPC组织和 17例鼻咽慢性炎症组织中HSPs和 p5 3的表达。 结果 :HSP 2 7和 p5 3在NPC组织中表达升高 ,与鼻咽炎症组织比较 ,差异有显著性意义 (P <0 .0 5 ) ;但在NPC的组织分型和临床分期之间 ,差异无显著性意义 (P >0 .0 5 )。HSP 90和HSP 70在NPC组织和慢性炎症组织间差异无显著性意义 (P>0 .0 5 )。结论 :HSPs和 p5 3在NPC组织中存在一定程度的异常表达 ,提示其在NPC的发病机制中可能发挥一定作用     

p53 codon 72 polymorphism association with head and neck squamous cell carcinoma

p53 tumoral suppressor gene harbors a functional polymorphism which codes either arginine (Arg) or proline (Pro) in the protein p53 of codon 72. Such polymorphism has been associated with the development or prognosis of head and neck squamous cell carcinoma (HNSCC).Aim: we assessed codon 72 p53 allelic frequencies and genotypes in HNSCC Iranian patients.Study design: Case Study.Materials and Methods: a total of 132 HNSCC patients and 123 healthy controls were genotyped. DNA source was from mononuclear cells of the peripheral blood. DNA amplification was done by means of the allele-specific polymerase chain reaction.Results: genotypes and allele distribution were not significantly different between patients and controls. Moreover, no statistically significant association was found between the 72 and p53 codon tumor location, gender or age at the time of diagnosis. However, the Pro/Pro genotype was significantly increase in stage IV patients (30.8%) when compared to stages I-III of the disease (11.1%) (p=0.03), and a significantly higher percentage of patients with the Pro allele had and a risk increase in stage IV disease (OR=2.2, 95% CI=1.2-4.2, p=0.01).Conclusion: data revealed that the p53 polymorphism do not impact the risk of HNSCC in Iranians, nonetheless, it can affect tumor progression to a higher tumor stage.     

p53蛋白在喉鳞癌及癌旁组织中表达的研究

应用抗ｐ５３单克隆抗休琢ＬＳＡＢ免疫组织化学染色法检测喉鳞癌，喉癌旁组织及声带息肉ｐ５３蛋白的表达。结果显示：２５例喉鳞癌呈阳性反应，４例距肿瘤边缘〈０．５ｃｍ的喉癌旁组织呈弱阳以应，２０例距肿瘤边缘〉２ｃｍ的喉癌旁组织及１６例声带息肉均为阴性。     

喉癌中maspin与p53表达的相关性

目的 观察喉癌中maspin和p53蛋白的表达,探讨maspin和p53在喉癌发生、发展中的作用。方法 采用免疫组化法检测78例喉鳞癌组织中maspin和p53蛋白。结果 在喉癌中maspin阳性表达率为55.1%(43/78),maspin表达下降与病理分化程度低、淋巴结转移有关。p53阳性表达率为58.9%(46/78)。在maspin阳性表达的43例喉癌中,p53阳性表达率为79.1%,maspin阴性表达的喉癌中,p53阳性表达率为34.3%,差异有统计学意义(P<0.05)。Spearman等级相关分析显示,maspin在喉癌组织中的表达与p53呈负相关性,有统计学意义(rs=-0.381, P=0.006)。结论 maspin在喉癌的发生发展中起一定抑制作用。喉癌中maspin表达与p53表达呈负相关,maspin可能是p53的效应基因。     

重组人p53腺病毒注射液（今又生）联合放疗治疗复发性鼻咽癌疗效观察

目的 观察重组人p53腺病毒注射液联合放疗治疗复发性鼻咽癌的疗效及不良反应。方法 以我院2005年1月至2006年12月期间收治的30例复发性鼻咽癌患者为研究对象。用非随机分组法将研究对象分为两组：实验组（15例）,采用重组人p53腺病毒注射液肿瘤局部多点注射联合放疗;对照组（15例）,采用经典放化同步治疗,分别于首次治疗后8周、6月、12月各随访1次,观察两组的疗效差异。通过CT测量肿瘤最大长径以确定肿瘤大小变化,并采用卡氏评分法评估患者生存质量。结果 重组人p53腺病毒注射液联合放疗对复发性鼻咽癌疗效满意,治愈率达20%,临床获益率为100%,除发热外,无其他严重不良反应,疗效及患者生存质量均明显优于放化同步治疗。结论 重组人p53腺病毒注射液联合放疗治疗复发性鼻咽癌安全、有效。     

Prognostic significance of p27 expression in carcinoma of the oral cavity and oropharynx.

OBJECTIVE: To study the role of p27, a cyclin-dependent kinase inhibitor, as a prognostic indicator in squamous cell carcinoma of the oral cavity and oropharynx. STUDY DESIGN: Retrospective review of 35 patients with squamous cell carcinoma of the oral cavity and oropharynx who presented to Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, between 1986 and 1995. METHODS: Inclusion criteria were the availability of clinical information, archival pretreatment biopsy material, and a minimum follow-up of 24 months. p27 staining was scored for frequency and intensity of tumor cell expression following immunoperoxidase staining using standard techniques. Samples of squamous epithelium from the uvula of 15 nonsmoking patients without past or present squamous cell carcinoma were used as normal controls. RESULTS: The association of p27 staining and other factors with response to treatment was evaluated by Fisher's Exact Test and with overall and disease-free survival by the Kaplan-Meier method with multivariate Cox regression. Low levels of p27 expression correlated significantly with unfavorable treatment response (P<.0001), shorter overall survival (P = .0001), and shorter disease-free survival (P = .003). Tumor site (alveolus) was also associated with shorter disease-free (though not overall) survival, but the association with p27 was independent of stage and site in multivariate analysis.     

Prognostic value of Survivin and Livin in nasopharyngeal carcinoma

BACKGROUND AND OBJECTIVES: Survivin and Livin are new members from the family of anti-apoptotic factors. Increased levels of Survivin and Livin have been observed in many malignancies and correlated with poor prognosis. Survivin is expressed almost exclusively in proliferating cells, including various kinds of cancers, but Livin expression is relatively rare in cancer cells. Therefore, the present study examines the expressions of Survivin and Livin in nasopharyngeal carcinoma (NPC) and investigates whether their expression contributes to the prognosis of NPC. METHODS: We investigated the expression of Survivin and Livin in 80 NPC samples using immunohistochemistry stain and correlated it with the survival of these patients using log-rank test and Cox multifactor regression analysis. RESULTS: All the patients were followed up at least for 60 months. During the following period, 21 cases developed distant metastasis, 9 cases developed local-regional recurrence, and 5 developed both distant metastasis and local-regional recurrence. Among them, 30 patients died of recurrence of tumor. In addition, the expression of Survivin was related with distant metastasis. Patients with low Survivin expression had better overall survival, disease-free survival and distant metastasis-free survival rates than the group with high Survivin expression (P = .0086, .0097, and .0318, respectively). Cox regression analysis confirmed that high Survivin expression was related to worse prognosis in NPC patients. However Livin expression level was not related with the survival of patients with NPC. CONCLUSION: NPC expresses high levels of Survivin and Livin, which may play an important role in the oncogenesis and tumor development. Over-expression of Survivin was related with poor prognosis. We suggest that the determination of Survivin expression may provide predictive information on NPC patients.     

喉癌人乳头瘤病毒感染和p53蛋白表达的研究

对４４例喉鳞癌和１６例声带息肉患者采用原位核酸杂交技术探测其人乳头瘤病毒（ＨＰＶ）６Ｂ，１１，１６，１８型ＤＮＡ同源序列及ＬＳＡＢ免疫组化法探测其Ｐ５３蛋白的表达，结果：（１）喉癌与ＨＰＶ１６／１８杂交阳性率为４３．２％（１９／４４），声带息肉为１２．５％（２／１６）（Ｐ〈０．０５）（２）喉癌ｐ５３蛋白阳性率为５６．８％（２５／４４），声带息肉全部为阴性；（３）喉癌ＨＰＶ１６／１８杂交及ｐ５３蛋白     

Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance

p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n= 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours.     

Prognostic significance of tumor volume in nasopharyngeal carcinoma

Objective

To investigate the prognostic significance of primary and residual tumor volume in nasopharyngeal carcinoma.

Methods

56 patients were included in the study. Diameters of tumors were measured from CT and MR film hardcopies. Diameter-based measurements were computed as an ellipsoid (V = 4/3·π·d1·d2·d3) to calculate diameter-based volume. It was investigated whether primary tumor volume provided prognostic information about local regional recurrence free survival (LRRFS), disease free survival (DFS), distant metastasis free survival (DMFS) and overall survival (OS) by monovariant and multivariant analysis. Kaplan-Meier survival analysis method and log-rank test were used to estimate survival analysis (95% confidence interval). Cox regression test was used for two variant and multivariant survival analysis. Statistical Package for Social Sciences (SSSP) 10.0 for Windows programme was used for data analysis.

Results

In the multivariate analysis, in the patients with tumor volume more than 60 ml, local regional recurrence more frequently developed. The relationship between tumor volume and local regional recurrence was found significant (p = 0.053). In the monovariate analysis, primary tumor volume was found to be a significant predictive value on DFS and DMFS. In the patients with tumor volume below 20 ml, DFS was 60%, whereas in the patients with tumor volume above 60 ml, DFS was 0% (p = 0.007). The prevalence were 68% and 0% in the patients group that had tumor volume below 30 ml and above 60 ml respectively. DMSF ratios in the patients with primary tumor volume below 20 ml and above 60 ml were 86.67% and 33.3% respectively. The residual tumor volume (RTV) at first control after treatment was found to be a significant prognostic factor on LRRFS (p = 0.03).

Conclusion

The foundation of new T staging systems that consists of PTV that was found as an independent prognostic factor alone in multivariate statistical analysis may precede better prediction of prognosis and more appropriate treatment of patients having different prognostic factors. RTV in the first control after treatment was a significant prognostic factor on LRRFS.     

A lack of association between p53 mutations and recurrent nasopharyngeal carcinomas refractory to radiotherapy

OBJECTIVE: The object of this study was to determine the incidence of p53 mutation in recurrent nasopharyngeal carcinoma refractory to radiotherapy. STUDY DESIGN: Prospective study. METHODS: There were 31 patients enrolled in this study between 1995 and 1998. All patients had received radiotherapy but none of them had undergone chemotherapy or local salvage surgery previously. RESULTS: The p53 status of each tumor was analyzed by polymerase chain reaction and by sequencing of exons 5 to 8 (codons 126-306). Five (16.1%) of 31 patients had mutations in the p53 gene, of which 2 were non-sense mutations, 2 were transition mutations, and 1 was a frameshift deletion mutation. The majority of the p53 mutations were found in exon 5. There is no significant difference in the incidence of p53 mutation compared with that of the previous reports for the primary disease. Based on the clinicopathologic data, there was no specific difference found between these 5 patients and the others. CONCLUSIONS: This study shows that p53 mutation is an infrequent event and may have no essential role in recurrent nasopharyngeal carcinomas.     

增殖细胞核抗原和p53基因在鼻咽癌中的表达及相关性研究

目的:通过免疫组织化学方法检测鼻咽癌(NPC)患者增殖细胞核抗原(PCNA)、p53基因表达,分析其与主要临床指标间的关系。方法:免疫组织化学检测鼻咽活检组织中PCNA、p53蛋白表达,并比较与分析两者和NPC临床分期及颈淋巴结转移的关系。结果:鼻咽部慢性炎性组织中p53阳性率为9.5%,明显低于NPC组织中的阳性率(76.3%)(P<0.01)。NPC伴颈淋巴结转移组p53阳性率(90.9%)明显高于无颈淋巴结转移组(57.7%)(P<0.01),临床Ⅱ、Ⅲ和Ⅳ期p53阳性率(分别为93.3%、80.0%和100.0%)均明显高于临床Ⅰ期(40.0%)(均P<0.01),且表达强度有增加的趋势。随着临床分期的增高,PCNA增殖指数(PI)分级有增高的趋势,NPC伴颈淋巴结转移组中PCNAPI之Ⅰ级所占比例较无颈淋巴结转移组下降,而Ⅱ、Ⅲ、Ⅳ级所占比例增加,但无统计学意义,NPC组织中PCNA表达与p53表达显著相关(P<0.01)。结论:p53蛋白可作为NPC较好的肿瘤标记物,p53阳性的NPC患者较易发生颈淋巴结转移,随着NPC病程的发展,p53表达率及表达强度均增加,PCNAPI可反映NPC的增殖状况,可能与预后相关。