喉鳞癌中增殖细胞核抗原和p53蛋白表达的临床意义及其相互关系

本文以ＬＳＡＢ免疫组化方法，用单克隆抗体ＰＣ１０和ＤＯ－１对３０例喉鳞癌及１０例对照组（声带息肉）的增殖细胞核抗原（ＰＣＮＡ）与ｐ５３蛋白表达进行研究，探讨其生物学意义。结果发现：１）喉鳞癌组织ＰＣＮＡ阳性表达率为１００％（ＰＣＮＡ－ＬＩｓ１６％～９２％），强阳性率为３６７％（１１／３０），对照组６例阴性，４例弱阳性表达（ＰＣＮＡ－ＬＩｓ＜１０％），试验组阳性表达率及表达程度明显高于对照组（Ｐ＜００５）。２）ｐ５３蛋白在喉鳞癌中阳性表达率为６６７％，对照组全部阴性，有显著差异（Ｐ＜００５）。３）在喉鳞癌组织中，ＰＣＮＡ和ｐ５３蛋白表达与临床分型、Ｔ分期及病理分化程度无显著关系（Ｐ＞００５），与淋巴转移及术后生存率关系密切（Ｐ＜００５）。４）ＰＣＮＡ与ｐ５３蛋白表达正相关。提示：１）喉鳞癌的增殖活性显著增强，ｐ５３基因突变与喉鳞癌的发生和发展有关。２）检测ＰＣＮＡ和ｐ５３蛋白有助于喉鳞癌的早期诊断和鉴别诊断，帮助治疗决策及判断预后。３）ｐ５３对ＰＣＮＡ有调节作用，为研究肿瘤的发生机理和寻找防治对策提供了新的理论依据。     

喉乳头状瘤HPV16/18感染与p53蛋白表达的相关性

目的：了解喉乳头状瘤组织内ＨＰＶ１６／１８的感染与抑癌基因ｐ５３变异的关系,以及ＨＰＶ感染在喉乳头状瘤发病中的作用。方法：采用ＰＣＲ和免疫组化技术,检测３５例喉乳头状瘤组织中ＨＰＶ１６／１８ＤＮＡ及ｐ５３蛋白的表达。结果：２４例组织中检出ＨＰＶ１６／１８ＤＮＡ（６８．６％）;１９例ｐ５３蛋白呈过度表达（５４．３％）;在１２例中同时检出ＨＰＶ１６／１８ＤＮＡ和ｐ５３蛋白过度表达（３４．３％）。结论：     

喉鳞癌中增殖细胞核抗原和p53蛋白表达的临床意义及其…

本文以ＬＳＡＢ免疫组化方法，用单克隆抗体ＰＣ１０和ＤＯ－１对３０例喉鳞癌及１０例对照组（声带息肉）的增殖细胞核抗原（ＰＣＮＡ）与ｐ５３蛋白表达进行研究，探讨其生物学意义。结果表明；１）喉鳞癌组织ＰＣＮＡ阳性表达率为１００％（ＰＣＮＡ－Ｌｌｓ１６％～９２％），强阳性率为３６．７％（１１／３０），对照组６例阴性，４例弱阳性表达（ＰＣＮＡ－ＬＩｓ〈１０％），试验组阳性表达率及表达程度明显高于对照组（Ｐ〉     

MDM 2基因在鼻咽癌中的表达及其与p53蛋白表达、EB病毒潜伏感染的关系

目的：探讨ＭＤＭ２基因在鼻咽癌（ＮＰＣ）中的表达情况及其与ｐ５３蛋白表达、ＥＢ病毒（ＥＢＶ）潜伏感染的关系。方法：运用非同位素原位杂交、免疫组化和多聚酶链反应技术对４６例ＮＰＣ、１２例慢性鼻咽炎症粘膜（ＣＩＮＥ）分别进行ＭＤＭ２ｍＲＮＡ、ＭＤＭ２蛋白、ｐ５３蛋白及ＥＢＶ－ＤＮＡ的检测。结果：４６例ＮＰＣ中,１４例ｍＲＮＡ及ＭＤＭ２蛋白高表达,３８例为ｐ５３蛋白阳性,４３例为ＥＢＶ－ＤＮＡ阳性,１２     

鼻内翻性乳头状瘤及其癌变与p53蛋白异常表达

目的：探讨鼻内翻性乳头状瘤及其癌变与ｐ５３基因的关系。方法：采用免疫组化方法（ＡＢＣ法）对３６例鼻内翻性乳头状瘤（ＩＰ）组织和１６例鼻内翻性乳头状瘤癌变（ＩＰ＋ＳＣＣ）组织进行了ｐ５３蛋白检测。结果：３６例ＩＰ均为ｐ５３蛋白阴性，而在１６例ＩＰ＋ＳＣＣ组织中有５例为ｐ５３蛋白阳性，阳性率为３１．３％（５／１６），经统计学处理，二者差异显著（Ｐ〈０．００１）。结论：ｐ５３蛋白异常表达可能与ＩＰ的发生     

鼻咽癌组织中p53基因突变及与EBV感染的关系

我们采用聚合酶链反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）技术，对ｐ５３基因突变情况进行检测和分析，以探讨ＥＢＶ与ｐ５３基因突变的关系。１　材料与方法标本：２１例鼻咽癌活检组织来自本院耳鼻咽喉科，全部患者未接受过放射治疗。病理检查均为低分化鳞状细胞癌。以５例鼻咽炎组织作对照。新鲜组织标本液氮冷冻，－７０℃冰箱保存。ＤＮＡ提取：按ＤＮＡ提取药盒（中山医科大学达安基因诊断中心提供）方法提取标本组织ＤＮＡ。ｐ５３基因的ＰＣＲ扩增：ｐ５３基因第５、６、７、８外显子引物设计为：ｐ５３－５Ｆ：５′－ｃｔｃｔｇ…     

上颌窦鳞癌两种癌基因及增殖细胞核抗原的表达及意义

目的检测上颌窦鳞癌、上颌窦内翻性乳头状瘤及上颌窦炎性粘膜中ｒａｓ、ｐ５３及增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ，ＰＣＮＡ）的表达情况，并分析其表达与上颌窦鳞癌临床病理特性和预后的关系。方法应用免疫组织化学方法检测４０例上颌窦鳞癌、２０例上颌窦内翻性乳头状瘤、１０例上颌窦炎性粘膜中ｒａｓ、ｐ５３、ＰＣＮＡ的表达情况。结果ｒａｓ基因表达与上颌窦鳞癌分化程度有关，其表达多见于高分化鳞癌中；ｐ５３基因表达只出现在上颌窦鳞癌中，在上颌窦内翻性乳头状瘤及炎性粘膜中无ｐ５３基因的表达；高ＰＣＮＡ指数上颌窦鳞癌较低ＰＣＮＡ指数者预后为差。结论ｐ５３基因表达可能作为上颌窦鳞癌诊断的标志物之一，ＰＣＮＡ指数可作为上颌窦鳞癌预后的参考指标，并可作为指导上颌窦鳞癌治疗的参考。     

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     

鼻咽癌肿瘤c—myc基因表达及p16基因失活的研究

目的 以原发性鼻咽癌为研究对象,探讨ｐ１６抑癌基因,ｍｙｃ家族癌基因在鼻咽癌发生、发展及其生物学行为的变化规律。方法 用多重聚合酶链反应（ｍｕｌｔｉｐｌｅ ｐｏｌｙｍｅｒａｓｅ ｃｈａｉｎ ｒｅａｃｔｉｏｎ,ＭＰＣＲ）,限制性内切酶ＰＣＲ、免疫组化及逆转录ＰＣＲ（ｒｅｖｅｒｓｅ ｔｒａｎｓｃｒｉｐｔａｓｅ ＰＣＲ,ＲＴ ＰＣＲ）方法,检测６９例鼻咽癌活检肿瘤组织中,Ｐ１６基因纯合缺失、甲基化、ｐ１６基因蛋白表达（免疫组化）、ｃ－ｍｙｃ基因表达等情况。结果 Ｐ１６基因纯合缺失７例,甲基化１１例,总失活率为２６．１％（１８／６９）。免疫组化检测ｐ１６基因蛋白表达阴性６０．９％（４２／６９）;阳性３９．１％（２７／６９）。ＲＴ ＰＣＲ,ｍｙｃ基因检测表达结果７３．９％（５１／６９）,无表达者２６．１％（１８／６９）。     

多肿瘤抑制基因—p16在喉癌中的丢失研究

目的：探讨ｐ１６基因的缺失与人喉癌的发生、发展的关系。方法：应用ＲＴ－ＰＣＲ及免疫组化方法检测ｐ１６。结果：４４例喉癌患者中２３例存在ｐ１６的失活，失活率为５２．３％，ｐ１６基因的失表达与喉癌的组织学分化程度及临床分期有密切关系（Ｐ＜０．０５），表明ｐ１６基因的变异有可能与人喉癌的发生发展有关，提示检测ｐ１６基因的丢失对于判断喉癌的恶性度及估计病情的进展具有重要意义。结论：随着对ｐ１６基因的不断了解，将为肿瘤的临床诊断、基因治疗提供新的思路和线索。     

p15和p27蛋白在鼻咽癌中的表达及其相关意义

目的研究周期素依赖激酶蛋白质类p15和p27蛋白在鼻咽癌（nasopharyngeal carcinoma,NPC）组织中的表达,探讨它们之间的关系与NPC生物学行为及预后的相关性。方法应用免疫组织化学EnVision两步法检测43例NPC组织和21例鼻咽黏膜慢性炎症组织,即非癌鼻咽组织（non-tumor nasopharyngeal,NP）中p15和p27表达水平。结果①NPC组织中p15和p27阳性表达率分别为65.1%和69.7%,与NP组比较,差异有统计学意义（P〈0.05）;②p15和p27蛋白在NPC中的表达与NPC临床分期、淋巴结转移、脑神经侵犯及治疗后5年生存率无关（P〉0.05）;③p15、p27阳性表达之间有相关性（P〈0.05）。结论p15蛋白和p27蛋白的表达缺失对NPC的发生起一定作用。     

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。     

鼻咽癌组织中bcl-2及P53蛋白表达的研究

目的 探讨bcl-2和P^53蛋白在鼻咽癌发生发展中的作用。方法 采用抗bcl-2和P^53蛋白的单克隆抗体，对25例鼻咽癌（Nasopharyngeal carcinoma,NPC)标本和16例正常鼻咽上皮（Nasopharyngeal epithelia,NE)标本进行免疫组化检测。结果 bcl-2和P^53蛋白的阳性表达率在鼻咽癌组织中分别为84．0％（21／25）和76．0％（19／25），与正常鼻咽上皮组相比差异有极显著性意义（P＜0．005）；鼻咽癌中有16例同时表达bcl-2和P^53蛋白。此外，bcl-2蛋白多见于分化差的鼻咽癌，而P^53蛋白则在相对分化较好的鼻咽癌中较多。结论 bcl-2原癌基因和P53抑癌基因在鼻咽癌的发病中可能有不同的意义，二种基因的协同作用可能与鼻咽癌持续生长有关。     

bcl-2、P 5 3基因及Epstein-Barr病毒在鼻咽癌中的表达

目的探讨鼻咽癌组织中p53、bcl-2、EBV表达情况及与主要临床指标间关系.方法免疫组化检测p53、bcl-2蛋白,多聚酶链反应(PCR)检测EBV.结果慢性炎性组织中p53、bcl-2及EBV阳性率分别为7.7%、23.1%和7.7%,明显低于鼻咽癌组织中的阳性率(分别为75.9%、88.9%和87.0%)(P<0.01).三者在鼻咽癌组织中共同阳性率为72.2%,p53、bcl-2明显正相关(r＝0.78,P<0.01).鼻咽癌伴颈淋巴结转移组p53阳性率(90.0%)明显高于无颈淋巴结转移组(58.3%)(P<0.01),临床Ⅱ、Ⅲ和Ⅳ期p53阳性率(分别为92.9%、78.9%和100%)均明显高于临床I期(38.5%)(P<0.01),且表达强度有增加的趋势.结论p53、bcl-2及EBV可作为鼻咽癌早期诊断的辅助指标之一,p53阳性的鼻咽癌患者较易发生颈淋巴结转移,随着鼻咽癌病程的发展,p53表达率及表达强度均增加,三者在鼻咽癌发生发展中起着重要作用.     

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).     

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     

Expression of p16, nm23-H1, E-cadherin, and CD44 gene products and their significance in nasopharyngeal carcinoma

OBJECTIVE: The present study was aimed to determine whether p16/MTS1, nm23-H1, E-cadherin, and CD44 proteins were expressed in nasopharyngeal carcinoma (NPC) and whether those expressions were pathologically significant in the progress of NPC. METHOD: We examined non-cancerous nasopharyngeal mucosa (20 cases) and NPC (80 cases) using immunohistochemistry with six different types of monoclonal antibodies against p16, nm23-H1, E-cadherin, CD44H, CD44v3, and CD44v6 proteins. RESULTS: The results showed that 1) the rates of positive p16 protein expression and of preserved E-cadherin protein expression in NPC were significantly lower than those in non-cancerous tissue (P <.01); 2) no significant difference in the rate of positive expression of nm23-H1, CD44H, CD44v3, and CD44v6 proteins were observed between non-cancerous nasopharyngeal mucosa and NPC; 3) no significant difference in the expression of those proteins were found by respective correlation analyses of sex, stage, and size of primary tumor in NPC; and 4) no significant difference in the rates of positive expression of CD44H, CD44v3, and CD44v6 proteins were observed in NPC between with and without lymph node metastasis, indicating that those gene products did not correlate with lymph node metastasis in NPC. However, there were inverse correlations between the expression of p16, nm23-H1, or E-cadherin protein and lymph node metastasis (P <.05), indicating that the expression of p16, nm23-H1, and E-cadherin gene were related to the carcinogenesis and tumor progression of NPC. CONCLUSION: Detecting the expressions of those gene products may provide clinically valuable information for therapeutic strategy and for predicting the prognosis of patients with NPC.     

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。     

The prognostic value of proliferating cell nuclear antigen (PCNA) and p53 protein expression in patients with advanced nasopharyngeal carcinoma

CONCLUSION: p53 protein and proliferating cell nuclear antigen (PCNA) were not ideal prognostic indicators in advanced nasopharyngeal carcinoma (NPC). Further investigation in searching for other potential biomarkers is needed to enhance the prediction of treatment outcome. OBJECTIVE: To assess the prognostic significance of p53 protein and PCNA expression in patients with advanced NPC. PATIENTS AND METHODS: This study included 46 patients with advanced NPC who had received treatment and regular follow-up for at least 5 years. We used immunohistochemistry (IHC) staining to assess p53 protein expression and PCNA labeling index, and correlate them with pathological subtypes, TNM stage, the presence of locoregional recurrence, and 5-year survival rate. RESULTS: p53 nuclear staining was positive in 32 patients (69.6%). All cases had positive PCNA nuclear staining with labeling index (LI) ranging from 6.5% to 92.9% (mean 53.4%). Only advanced T stage was found to be associated with high PCNA LI. Overexpression of p53 and PCNA LI had no impact on 5-year survival in this study group.