喉癌癌变过程中Cyclin E的表达及临床病理学意义

目的:研究喉癌癌变过程中Cyclin E的临床病理学意义.方法:用免疫组化检测20例正常喉粘膜,40例喉不典型增生和60例喉癌组织中Cyclin E的表达.结果:Cyclin E阳性表达定位于肿瘤细胞核.在喉癌癌变过程中,喉正常粘膜、不典型增生病变和喉癌中Cyclin E阳性表达率分别为:5.0%(1/20),20.0%(8/40)和45.0%(27/60)(P＜0.001).喉癌淋巴结转移组Cyclin E阳性表达率明显高于非淋巴结转移组.结论:Cyclin E异常表达可能是喉癌发生中早期分子事件,对喉癌发展起重要作用.     

喉鳞癌中P21 WAF1/CIP1、C-erbB-2的表达及其临床意义

目的研究喉鳞癌组织中P21WAF1/CIP1、C-erbB-2的表达,探讨它们在喉鳞癌的增殖、侵袭、转移中的作用.方法选取60例喉鳞癌作为研究对象,15例声带息肉组织作为对照,所有标本均切片作HE染色.用链霉素亲生物素-过氧化酶法(s-P法)研究肿瘤及声带息肉组织中P21WAF1/CIP1和C-erbB-2蛋白的表达,显微镜下计数阳性细胞,并分析阳性细胞百分率.结果(1)P21WAF1/CIP1在声带息肉组织中低表达,在喉癌组织中高表达,二者阳性率差异有显著性(P＜0.05);P21WAF1/CIP1在喉癌组织中的表达与肿瘤组织分级(P＜0.05)及临床分期(P＜0.05)有关,与年龄、性别、肿瘤部位及有无淋巴结转移无显著相关性;(2)C-erbB-2在声带息肉组织中低表达,在喉鳞癌中高表达,两者差异有显著性(P＜0.05);C-erbB-2在喉癌组织中的表达与各临床病理因素无显著相关;(3)经Spearman等级相关分析,P21WAF1/CIP1、C-erbB-2在喉鳞癌中表达呈正相关(P＜0.05).结论P21WAF1/CIP1可以作为一种独立的预后预测因子;C-erbB-2在某种程度上反应了肿瘤的生长特性,但不能判断喉癌预后;在喉鳞癌中P21WAF1/CIP1和C-erbB-2间存在正调控机制.     

CyclinD1和P21WAFI/CIP1在喉癌变过程中的表达及其临床病理意义

为探讨喉癌变过程中CyclinD1和P21WAFI/CIP1表达的临床病理学意义,用免疫组化检测20例正常粘膜、40例不典型增生病变和60例喉癌组织中CyclinD1和P21WAFI/CIP1的表达.结果是:(1)CyclinD1和P21WAFI/CIP1阳性表达定位于细胞核;(2)在喉癌变过程中,喉正常粘膜、不典型增生病变和喉癌中CyclinD1阳性表达率分别为5.0%(1/20),30.0%(12/40),53.3%(32/60)(P＜0.001);P21WAFI/CIP1阳性表达率分别为95.0%(19/20),75.0%(30/40)和63.3%(38/60)(P＜0.05);(3)P21WAFI/CIP1在高、中、低分化的喉癌中阳性表达率分别为76.2%(16/21),65.5%(19/29)和30.0%(3/10)(P＜0.05);P21WAFI/CIP1阳性表达与肿瘤细胞的分化有关;(4)CyclinD1和P21WAFI/CIP1阳性表达显著相关.表明:(1)喉癌变过程中CyclinD1阳性表达率呈逐渐升高的趋势,而P21WAFI/CIP1阳性表达率呈逐渐降低的趋势;(2)CyclinD1异常表达是喉癌发生中早期分子事件;(3)P21WAFI/CIP1表达与喉癌细胞分化程度有关;(4)CyclinD1和P21WAFI/CIP1阳性表达显著相关.     

喉癌中环氧化酶-2和p53的表达及相关性研究

目的 :了解喉癌组织中环氧化酶 2 (Cox 2 )及p5 3的表达 ,探讨Cox 2在喉癌发生发展中的作用及与p5 3之间的关系。 方法 :采用免疫组织化学方法检测 6 3例喉癌组织中Cox 2与 p5 3的表达情况。 结果 :6 3例喉癌标本中Cox 2阳性表达率为 5 8.7% (37/6 3) ,患者的不同临床分期的表达差异有统计学意义 (P <0 .0 5 )。p5 3的阳性表达率为 6 3.5 % (4 0 /6 3) ,不同组织病理学分级的 p5 3阳性表达的差异有统计学意义 (P <0 .0 5 ) ;Cox 2与p5 3之间存在等级相关性。结论 :Cox 2能促进喉癌的生长、增殖与浸润 ,应用Cox 2抑制剂可望对喉癌的发展起到抑制作用     

甲状腺癌p53调节基因Mdm2以及p21WAF/CIP1蛋白的表达

目的探讨p53、鼠双微体2(murinedonbleminute2,Mdm2)及p21WAF/CIP1等蛋白在甲状腺癌组织中的表达、意义及相互作用关系。方法取甲状腺癌、癌旁与良性病变组织构建组织芯片,应用免疫组化方法检测p53、Mdm2及p21WAF/CIP1在甲状腺良恶性病变中的表达。结果p53、Mdm2及p21WAF/CIP1在甲状腺癌中表达的阳性率分别为50.6%(37/73),63.0%(47/73)和38.4%(28/73)。同癌旁组织相比,p53和Mdm2表达明显升高(P<0.01),而p21WAF/CIP1的表达明显降低(P<0.05)。p21WAF/CIP1和p53的阳性表达均与未分化癌、有无淋巴结转移及受累程度显著相关(P<0.05);Mdm2的阳性表达与甲状腺良恶性病变显著相关(P<0.05)。三者阳性表达两两之间统计学上具有关联性(P<0.05)。结论p53和Mdm2的过表达以及p21WAF/CIP1的缺失表达可能会导致甲状腺癌的恶性形成和进展;三者中蛋白主要以p53-Mdm2-p21WAF/CIP1通路的方式作用于细胞的转化和肿瘤的形成;联合检测p53和Mdm2的表达可用于评定甲状腺癌的恶性程度。检测p21WAF/CIP在甲状腺癌中表达的变化可用于评估其生物学行为和判断预后。     

抑癌基因p15、Rb在喉鳞状细胞癌中表达的研究

目的 :研究抑癌基因p15、Rb蛋白表达对喉鳞状细胞癌诊断、治疗及预后判断的意义。方法 :用免疫组化SABC法检测喉癌组 45例石蜡标本与对照组 15例喉部正常或增生的黏膜上皮标本的 p15、Rb蛋白表达情况。结果 :喉鳞状细胞癌组p15蛋白阳性率 (48.9%)与对照组阳性率 (10 0 .0 %)比较 ,差异有极显著性意义 (P<0 .0 1) ;喉癌组中 0～Ⅱ期 p15蛋白阳性率 (6 6 .7%)与Ⅲ～Ⅳ期阳性率 (33.3%)比较 ,差异有显著性意义 (P <0 .0 5 ) ;喉癌组Rb蛋白阳性率 (88.9%)与对照组阳性率 (93.3%)比较 ,差异无显著性意义 (P >0 .0 5 ) ;2× 2列联表 χ2 检验 ,p15、Rb蛋白表达无相关性 (P >0 .0 5 ) ;对照组中 ,p15蛋白的表达以鳞状上皮组织中远离基膜的棘层细胞、颗粒层细胞明显 ,而Rb蛋白的表达则以基底层细胞及近侧棘层细胞明显。结论 :抑癌基因 p15的表达缺失对喉鳞状细胞癌的发生、发展有一定的作用 ,p15蛋白的检测对喉鳞状细胞癌的治疗及估计预后有指导意义 ;喉鳞状细胞癌组织中 p15、Rb的蛋白表达无相关性 ;正常及增生的喉部鳞状上皮的细胞层次间 ,p15、Rb蛋白表达不一致 ,p15蛋白表达对细胞增殖有抑制作用。     

缝隙连接蛋白43和E-钙黏附素表达与喉癌生物学行为关系的研究

目的　研究缝隙连接蛋白基因 4 3(connexin4 3,Cx4 3)和E 钙黏附素 (E cadherin ,E cad)在喉癌组织中的表达与其生物学行为的关系 ,探讨喉癌发生、发展的机制。方法　应用免疫组织化学PicTureTM二步法 ,检测有 5年以上随访资料的 6 0例喉癌组织和 10例癌周正常喉组织中Cx4 3和E cad的表达 ,结果进行统计学处理。结果　Cx4 3和E cad蛋白主要定位于细胞膜上 ,10例癌周正常喉黏膜组织均呈阳性表达。 6 0例喉癌患者中 ,70 0 % (4 2 / 6 0例 )的喉癌Cx4 3呈阳性表达 ,按喉癌的临床分期、颈部淋巴结转移、喉癌复发情况分组差异有显著性意义 (χ2 =5 11、6 4 1、3 86 ,P值均 <0 0 5 ) ,与喉癌的组织学分级差异有极显著性 (χ2 =15 0 9,P <0 0 1) ,与喉癌患者的生存期无统计学意义 (χ2 =2 6 5 ,P >0 0 5 ) ;4 1 7% (2 5 / 6 0例 )的喉癌组织中E cad表达减低 ,按喉癌的临床分期、喉癌复发情况分组及生存期分组差异有显著性意义 (χ2 =6 0 9、5 35、5 14 ,P值均 <0 0 5 ) ,与喉癌的组织学分级、颈部淋巴结转移差异有极显著性意义 (χ2 =15 0 7、6 6 5 ,P均值 <0 0 1)。同一标本中Cx4 3和E cad基因表达有显著的相关性和一致性 (r=0 6 3,P <0 0 0 0 1)。结论　喉癌存在Cx4 3和E cad基因的失活及蛋     

p16、COX-2在喉癌组织中的表达及相关性研究

目的 研究喉癌组织中抑癌基因p16及环氧化酶-2(COX-2)的表达,探讨p16、COX-2在喉癌发生发展中的作用及两者之间的关系.方法 采用免疫组织化学方法检测50例喉癌组织中p16、Cox-2的表达情况.结果 50例喉癌标本中喉癌中p16蛋白表达的阳性率为56.0%,正常喉黏膜中阳性表达率为80.0%,p16蛋白在喉鳞癌组织中的阳性表达率明显低于正常喉黏膜组织(P<0.05),有统计学意义.随着临床分期的进展及组织学分化程度的降低,p16蛋白表达进一步降低.COX-2在喉癌组织中高表达,阳性表达率为62.0%,正常组织阳性率为24%,患者的不同临床分期的表达差异有统计学意义(P<0.05).p16与COX-2之间存在负相关性.结论 两者的联合检测对估计喉癌的恶性度,判断预后有FINDINGS REPORT定意义.     

p21WAF1/CIP1和抑制增殖细胞核抗原的表达与下咽癌及喉癌的临床关系

目的：探讨p21^WAF1/CIP1和抑制增殖细胞核抗原(PCNA)的表达与下咽癌、喉癌的分级、转移及预后的关系,了解p21^WAF1/CIP1在下咽癌、喉癌发生、发展中的作用以及与PCNA的相关性。方法：对45例下咽癌、25例声门上型喉癌、23例声门型喉癌标本,用Envision HIS的方法检测p21^WAF1/CIP1、PCNA的表达情况,并分析p21^WAF1/CIP1表达与下咽癌、喉癌临床病理特征、转移、复发和预后的关系。结果：p21^WAF1/CIP1阳性表达率为51.6％(48／93),PCNA的阳性表达率为97.8％(91／93);p21^WAF1/CIP1表达与下咽癌、喉癌患者的年龄、性别、肿瘤分化、远处转移及复发无显著性相关,与肿瘤的原发部位的T分期有显著性相关;p2^WAF1/CIP1的表达还与肿瘤的预后有显著性相关;而PCNA与肿瘤的临床分期及淋巴转移有显著性相关,p21^WAF1/CIP1与PCNA的表达具有相关性。结论：p21^WAF1/CIP1、PCNA是预测肿瘤浸润范围及转移的良好指标,p21^WAF1/CIP1对预后的判定具有一定的指导意义。     

喉鳞状细胞癌中PTEN和Caspase-3的表达及临床意义

目的 :研究抑癌基因PTEN和半胱氨酸蛋白酶Caspase 3在喉鳞状细胞癌中的表达及临床意义。 方法 :应用免疫组织化学SP法检测 2 0例正常喉组织、6 0例声带不典型增生、2 89例喉癌组织中PTEN ,Caspase 3的表达。结果 :正常喉组织、声带不典型增生、喉癌组织中PTEN阳性表达率分别为 10 0 .0 %、86 .7%、5 8.8% ,三者之间差异具有统计学意义 (均 P <0 .0 5 ) ;Caspase 3阳性表达率分别为 85 .0 %、6 1.7%、4 8.1% ,三者之间差异具有统计学意义 (均P <0 .0 5 )。另外 ,Caspase 3与PTEN在喉癌中的表达具有正相关性 (P <0 .0 1)。结论 :喉鳞状细胞癌中抑癌基因PTEN ,Caspase 3的表达异常可能与喉癌的发生、发展有关。     

Prognostic significance of p21WAF1/CIP1 expression in tongue squamous cell carcinomas

OBJECTIVE: To investigate the prognostic significance of p21(WAF1/CIP1) expression and its relationship with p53 accumulation and other apoptotic markers such as Bax, Bcl-2, and apoptotic index in relation to disease-specific survival in oral tongue squamous cell carcinoma (SCC). DESIGN: A 10-year retrospective clinical study. Information about clinical findings, treatment, and follow-up has been recorded prospectively. PATIENTS AND METHODS: Diagnostic, formalin-fixed, paraffin-embedded sections taken from 80 randomly selected patients before treatment for T1 to T4 oral tongue SCC were stained immunohistochemically with p21(WAF1/CIP1). The percentages of positive nuclei that stained positive for tumor were determined. MAIN OUTCOME MEASURES: The significance of prognostic parameters was tested by log-rank and Kaplan-Meier methods for the univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Expression of p21(WAF1/CIP1) correlated inversely with T classification and clinical stage (P =.02 and P =.006, respectively) but not with N classification, tumor differentiation, or apoptosis-related variables such as p53 accumulation, apoptotic index, and Bax and Bcl-2 expression. Patients with tumors expressing high p21(WAF1/CIP1) values had increased disease-specific survival time (P =.03). The correlation between p21(WAF1/CIP1) expression and disease-specific survival was even more significant when restricted to p53-negative tumors (P =.002). A 2-parameter combination between p21(WAF1/CIP1) expression and Bax expression or p21(WAF1/CIP1) expression and p53 accumulation, respectively, revealed an enhanced prognostic potential (P<.001) when compared with single parameters. CONCLUSION: The expression of p21(WAF1/CIP1), particularly in combination with p53 accumulation or Bax expression, has prognostic value in oral tongue SCC.     

Expression of p53, p21 CIP1/WAF1 and eIF4E in the adjacent tissues of oral squamous cell carcinoma: establishing the molecular boundary and a cancer progression model

The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma (OSCC) and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T (cancer), P1 (0–0.5 cm), P2 (0.5–1 cm), P3 (1–1.5 cm) and P4 (1.5–2 cm) groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21 ^CIP1/WAF1 , eIF4E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining. Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21 ^CIP1/WAF1 expression displayed an opposite trend. eIF4E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression.     

Expression of cell cycle regulators in squamous cell carcinoma of maxillary sinus and their significance]

OBJECTIVE: To investigate the clinicopathlogical significance of cyclinE, cyclinD1, P21WAF1/CIP1 and P27KIP1 expression in squamous cell carcinoma of maxillary sinus. METHODS: The expression of cyclinE, cyclinD1, P21WAF1/CIP1 and P27KIP1 was examined by the method of immunohistochemistry in inflammatory mucosa of maxillary sinus(10), inverting papilloma of maxillary sinus(20) and squamous cell carcinoma of maxillary sinus (50). RESULTS: (1) In inflammatory mucosa, inverting papilloma and squamous cell carcinoma, the positive immunostaining rates of cyclinD1 protein were 10.0%, 25.0%, 48.0% respectively (P < 0.05); cyclinE protein was 20.0%, 35.0%, 58.0% respectively (P < 0.05); P21WAF1/CIP1 protein was 80.0%, 65.0%, 40.0% respectively (P < 0.05) and P27KIP1 protein was 70.0%, 75.0%, 40.0% respectively (P < 0.05). (2) There was no significance between the clinical type, T stage and clinical stage of carcinoma of maxillary sinus and the expression of cyclinD1, cyclinE, P21WAF1/CIP1 and P27KIP1 (P > 0.05). (3) P21WAF1/CIP1 positive expression in highly, moderately and poorly differtiated carcinomas were 73.2% (11/15), 58.9% (11/19), 25.0% (4/16) respectively (P < 0.05). CONCLUSION: (1) With the development of the lesion, the positive immunostaining rate of cyclinE and cyclinD1 protein increases, while the rate of P21WAF1/CIP1 and P27KIP1 protein decreases. (2) P21WAF1/CIP1 expression is associated with tumour cell differentiation. (3) The mutual mechenism of cell cycle regulators plays an important role in the squamous cell carcinoma of maxillary sinus. The quantity and the frequency of four kinds of gene expression increase with the progression of maxillary sinus carcinogenesis.     

喉癌前病变p53过度表达的研究

采用标记链霉菌素－生物素免疫酶技术结合微波炉处理方法，对１５例成人型喉头状瘤，１０例喉部不典型增生，２例喉原位癌，１０例声带息肉以及６例正常喉的组织标本进行了检测，结果发现：在７３．３％喉乳头状瘤，４０％喉不典型增生和５０％喉原位癌中检测到ｐ５３蛋白过度表达，而１０例声带息肉和６例中正常组织无一例出现ｐ５３的过度表达。     

Expression of cyclin‐dependent kinase inhibitor p21(WAF1) and p53 tumour suppressor gene in laryngeal cancer

The prognostic value of the expression of the cyclin‐dependent kinase inhibitor p21 and the p53 tumour suppressor gene was examined using immunohistochemistry in 60 patients with laryngeal cancer. Multivariate analysis using Cox's proportional hazard method, showed that p21 expression (P = 0.02) and advanced T stage (P = 0.003) significantly predicted survival. It was concluded that p21 expression may be a useful prognostic indicator in laryngeal cancer.     

The immunohistochemical expression of p21WAF1/Cip1 and Proliferating cell nuclear antigen in laryngeal squamous cell carcinomas

The purpose of this study was to assess the significance of the expression of p21WAF1/Cip1 and proliferating cell nuclear antigen (PCNA) in human laryngeal squamous cell carcinomas. Forty-eight patients (25 supraglottic, 23 glottic) who had undergone operations between 1998 and 2003 were included in this study. The Envision immunohistochemistry method was utilized to stain these tissue specimens. The results showed that the immunostaining of p21WAF1/Cip1 do not show any correlation with differentiation, N stage, metastasis, survival, recurrence or the laryngeal site of involvement. A significant inverse correlation was detected between p21WAF1/Cip1 and the T stage. In contrast, the percentage of PCNA labelled cells showed a significant correlation with the T stage, but not with other clinicopathological parameters. There were differences in the expression of p21WAF1/Cip1 and PCNA between the supraglottic and the glottic carcinomas. In conclusion, our findings suggest that p21WAF1/Cip1 and PCNA may play an important role in the progression of carcinoma of the supraglottic larynx.     

表皮生长因子受体为靶向的多肽基因导入系统介导 p21 WAF1对人喉癌的基因治疗

目的：评价靶向性非病毒载体系统介导的p21^WAF1对人喉癌基因治疗的可行性和有效性。方法：利用组建的表皮生长因子受体(EGF-R)介导的多肽基因导入系统与p21^WAF1基因构成基因载体复元物，分别体外转染人喉癌Hep-2细胞，通过荧光显微镜观察和通过转染喉癌细胞生长曲线及流式细胞仪检测等方法观察新的受体介导多肽基因导入系统对外源基因的导入和导入后对人喉癌细胞的抑制作用。结果：荧光显微镜观察到标记基因的表达产物绿色荧光蛋白，转染后48h呈弱阳性，72h呈强阳性；p21^WAF1基因转染后喉癌细胞生长受到明显抑制，第4天抑制率为79％；流式细胞仪检测到p21^WAF1转染的Hep-2细胞发生了明显的凋亡。结论：EGF-R介导的多肽基因导入系统可靶向性地将治疗基因导入Hep-2人喉癌细胞，p21^WAF1基因可明显抑制Hep-2细胞的生长并有效诱导基因凋亡。     

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。