Survivin基因在喉癌组织中的表达

目的探讨Survivin基因在喉癌组织中的表达,并分析与p53基因的表达、微血管形成以及临床病理因素的关系。方法应用免疫组化SP法检测Survivin、p53、CD34蛋白在40例喉癌组织中的表达情况,并与临床病理资料一起进行统计分析。结果Survivin蛋白在正常喉黏膜组织中不表达,40例喉癌组织中23例表达阳性,占57.5%。在P53蛋白表达阳性、阴性的喉癌组织标本中,Survivin蛋白阳性率分别为73.1%(19/26)和28.6%(4/14)(P=0.007)。Survivin蛋白阳性表达的病例中,平均瘤内微血管密度明显高于Survivin蛋白阴性表达的病例(P<0.001)。Survivin蛋白异常表达与喉癌临床分期、病理分级、颈淋巴结病理转移有关。结论Survivin基因在喉癌中存在高表达,并与p53基因突变、肿瘤微血管形成关系密切,Survivin异常表达可能在喉癌发生、发展及转移过程中发挥重要的抗凋亡作用。     

喉癌中细胞凋亡与凋亡相关基因Survivin及p53的研究

细胞凋亡同肿瘤的发生、发展以及临床治疗关系密切。Survivin是凋亡抑制蛋白的一种,而p53是典型的抑癌基因,二者的表达异常可能是肿瘤发生、发展的重要因素。本研究应用DNA原位末端标记技术（Tunel）检测喉癌细胞凋亡指数（AI）,免疫组织化学方法检测喉癌组织Survivin、p53蛋白的表达,探讨喉癌组织中凋亡程度与临床病理参数及Survivin、p53表达的相关性,并对Survivin、p53在肿瘤发展中的作用进行探讨。     

p27、p53和Bcl－2蛋白在喉癌和切缘组织中的表达

目的研究p27、p53和Bcl-2在喉鳞状细胞癌和切缘中的表达及其临床意义。方法用Evision免疫组化两步法检测39例喉鳞状细胞癌和相对应的14例喉癌切缘组织中p27、p53和Bcl-2蛋白的表达情况。结果①39例喉癌组织中p27、p53和Bcl-2的阳性表达率分别为48.7%(19/39)、51.3%(20/39)和7.7%(3/39),且p27、p53和Bcl-2与喉鳞状细胞癌患者的年龄、病理分级、临床分期和预后无明显的相关性;②14例喉癌切缘组织中p27、p53和Bcl-2的阳性表达率分别为57.1%(8/14)、14.3%(2/14)和28.6%(4/14),且切缘中p27、p53和Bcl-2蛋白的表达与喉鳞状细胞癌患者的年龄、病理分级、临床分期无明显的相关性。切缘中p27蛋白的表达与预后相关,而切缘中p53和Bcl-2蛋白的表达与预后无关;③p53蛋白在14例喉癌和喉癌切缘组织中的表达有统计学意义(P=0.001)。Bcl-2蛋白在14例喉癌和切缘组织中的表达有统计学意义(P=0.031);④在喉鳞状细胞癌中p27、p53蛋白的表达无相关性。结论①p27、p53和Bcl-2与喉癌患者的年龄、淋巴结转移、分期等无明显的相关性;②p27在切缘中的表达与预后有一定相关性;③p53、Bcl-2蛋白在喉鳞状细胞癌组织和喉癌切缘中的表达有统计学意义;④在部分喉癌切缘中见p53蛋白表达可能与喉癌术后复发有一定的相关性。Bcl-2可能在分子水平提示正常细胞向喉癌细胞的恶性转化。     

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。     

喉鳞状细胞癌中BAG-1和 p53基因的表达及其临床意义

目的：研究BAG-1和p53基因在喉鳞状细胞癌组织中的表达,探讨BAG-1在喉鳞状细胞癌发生、发展中的作用及与p53的关系。方法：运用免疫组织化学SP技术,检测40例喉鳞状细胞癌组织,27例喉癌旁正常组织及20例声带息肉组织中BAG-1与p53的表达。结果：BAG-1在喉癌中表达阳性率为72．5％,较喉癌旁组织（18．5％）、声带息肉组织（20．0％）高（P〈0．05）,其表达与预后呈负相关（P〈0．05）;p53在喉癌中表达阳性率为65．0％,而在喉癌旁组织和声带息肉组织中均无表达,与在喉癌组织中的表达相比差异有统计学意义（P〈0．05）;其表达与病理分化程度、颈淋巴结转移及预后呈负相关（P〈0．05）;在喉癌组织中BAG-1与p53表达之间未见显著性相关（P〉0．05）。结论：BAG-1和p53基因的过度表达与喉鳞状细胞癌的发生、发展存在一定的关系。BAG-1可作为早期诊断喉癌的一种生物标记,尤其是细胞核BAG-1定位可作为一种不良预后的预测因子;p53表达与喉癌颈淋巴结转移有关,可单独作为喉癌的预后指标。     

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.     

喉癌组织中CD105标记的微血管密度VEGF及p53蛋白的相关性研究

目的:评价微血管密度(MVD)的临床意义,比较分析CD105、VEGF、p53蛋白之间的相关性,探讨三者在喉癌肿瘤血管生成中的相互关系及临床病理意义。方法:采用免疫组织化学技术检测以CD105标记的MVD(CD105-MVD)、VEGF、p53蛋白在喉癌组织中的表达。结果:40例喉癌组织CD105-MVD为14.90±7.40,明显高于对照组织(P<0.05);Ⅲ、Ⅳ期喉癌组织的MVD高于Ⅰ、Ⅱ期,颈淋巴结转移组高于无淋巴结转移组,其差异有统计学意义;VEGF阳性率77.5%。p53蛋白阳性率67.5%。VEGF表达与肿瘤的TNM分期及病理分化有显著相关性(P<0.05)。p53蛋白表达与淋巴结转移呈显著相关(P<0.05)。CD105-MVD与VEGF、p53蛋白之间呈明显正相关(r=0.641,P<0.01;r=0.534,P<0.01)。结论:CD105与肿瘤活性血管生成有密切联系,是肿瘤新生血管的标志;喉癌组织CD105标记MVD的测定可作为预测喉癌患者复发转移及评估预后的重要独立指标;喉癌中VEGF的表达、p53蛋白表达与CD105-MVD呈正相关,三者联合可作为判断喉癌侵袭转移及预后的重要指标。     

喉癌中p53蛋白与VEGF表达的相关性研究

目的检测、比较分析喉癌中p53蛋白与VEGF的表达及平均瘤内血管密度的相关性.方法采用S-P免疫组织化学的方法检测62例喉癌术后标本中p53蛋白和VEGF的表达,并计算其平均瘤内血管密度;同时采用SPSS统计软件分析p53蛋白与VEGF的表达及瘤内血管密度的相关性.结果 62例喉癌中,33例p53蛋白阳性,38例VEGF阳性,平均瘤内血管密度为(34.58±11.23)mv;p53蛋白阳性的33例中,25例VEGF表达阳性,平均瘤内血管密度为(39.65±10.66)mv;29例p53蛋白阴性的病例中,13例VEGF表达阳性,平均瘤内血管密度为(30.45±11.76)mv;统计学处理发现p53蛋白阳性的病例中,VEGF表达的阳性率高于p53阴性的病例,平均瘤内血管密度高于p53阴性的病例.结论喉癌中VEGF的表达、平均瘤内血管密度与p53蛋白的表达呈正相关,mut-p53基因可能具有促进喉癌中VEGF表达、促进喉癌中微血管形成,进而促进喉癌细胞的侵袭与转移的作用.     

PLOD2蛋白在喉癌组织中的表达及其与预后的关系

目的　研究前原胶原赖氨酸-2-酮戊二酸5-双加氧酶（Recombinant procollagen lysine-2-oxoglutarate-5-dioxygenase，PLOD2）蛋白在喉癌组织中的表达与患者临床病理特征的关系及其与预后的关系。方法　对114例喉癌患者肿瘤石蜡标本中PLOD2的表达情况采用免疫组化方法检测，并用χ2检验分析其与临床病理特征的关系、Kaplan-Meier法进行生存分析、Cox比例风险模型进行复发多因素分析。从病例中随机选出8例患者的新鲜冰冻标本，采用实时定量聚合酶链反应和蛋白质印迹方法对8例患者的肿瘤组织和癌旁正常组织中PLOD2的表达情况进行检测。结果　PLOD2蛋白与临床分期、T分级有关（P 均＜0.05）。实时定量聚合酶链反应中喉癌组织PLOD2蛋白的表达水平高于癌旁正常组织（P＜0.05）。蛋白质印迹方法中喉癌组织PLOD2蛋白表达水平要高于癌旁正常组织（P＜0.05）。Kaplan-Meier生存分析显示，PLOD2低表达与患者生存率有关（χ2=12.484，P＜0.001），多因素Cox回归分析显示，PLOD2蛋白表达和M分级是影响喉癌生长的 独立危险因素。结论　PLOD2蛋白表达的高低与临床分期、T分级呈正相关。PLOD2蛋白是影响喉癌生长的独立危险因素，PLOD2蛋白表达越高，患者预后越差生存率越低。PLOD2蛋白表达对喉癌的生长、预后可能起着重要作用，可能是判断喉癌生长和预后的一种新的分子标志物。     

SEMA3D在喉癌组织中的表达及临床意义

目的探讨喉癌组织中轴突导向因子3D(SEMA3D)的表达与患者临床病理特征和预后的关系。方法收集2015年1月—2016年12月经外科手术切除的喉癌组织及对应癌旁组织标本61例,应用免疫组化SP法检测SEMA3D的表达情况,并对SEMA3D与喉癌临床病理特征及预后的关系进行统计学分析。结果免疫组化SP法显示,SEMA3D在喉癌组织中的表达水平显著低于在癌旁正常组织中的表达水平（P<0.05）。SEMA3D表达与患者的临床分期和颈部淋巴结转移密切相关(P<0.05)。Kaplan Meier生存分析显示,SEMA3D表达与患者生存率具有相关性（P＜0.001）。单变量Log rank检验分析显示吸烟、临床分期、颈部淋巴结转移和SEAM3D表达与患者预后具有相关性,进一步行Cox多因素回归分析发现SEMA3D低表达是影响喉癌预后的独立危险因素。结论SEMA3D蛋白低表达是影响喉癌预后的独立危险因素。SEMA3D蛋白阳性表达的喉癌患者预后较好,有望成为喉癌患者预后评估的新的生物标志物。     

Prognostische Bedeutung der Expression von p53, bcl-2 und bax im Plattenepithelkarzinom des Larynx – Eine multivariate Analyse

BACKGROUND AND OBJECTIVE: Conventional clinicopathologic parameters do not accurately reflect the clinical outcome of patients with head and neck carcinoma. The establishment of additional prognostic factors that may give insight into the biologic features of a tumor is therefore an essential goal. The present study analyses the expression patterns of p53, bcl-2, and bax with regard to their relationships with conventional tumor parameters and to their prognostic significance in patients with laryngeal squamous cell carcinoma. PATIENTS/METHODS: Paraffin-embedded tissue sections of 88 primary laryngeal squamous cell carcinomas diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. The mean follow-up time was 45.9 months. RESULTS: Bcl-2 immunoreactivity was positively correlated with an advanced clinical stage, a high T category, regional lymph node metastasis, and a high histological grading. Significant relationship between clinicopathologic parameters and p53 or bax expression were not detectable. The age of the patients, advanced disease, positive bcl-2 expression, and a high level of p53 expression were significantly associated with shortened disease-specific survival in univariate analysis. In multivariate analysis, age, clinical stage, and p53 expression had independent prognostic value. CONCLUSIONS: Although expression of p53 and bcl-2 was found to be clinically relevant in univariate analysis, only p53 but not bcl-2 was an independent predictor of patient outcome. This superiority of p53 in multivariate analysis points to its central role within cell cycle and death regulation, with which it influences two important parameters of tumor progression.     

喉癌p53蛋白和EGFR的免疫组织化学检测及意义

应用ＬＳＡＢ免疫组织化学染色法，对３２例原发喉鳞状细胞和８例喉正常上皮组织中的ｐ５３蛋白和表皮生长因子受体做定位和定量研究。结果表明：ｐ５３蛋白在喉癌组织中的表达位于细胞核内，ＥＧＦＲ的表达位于胞浆和核膜；喉癌组织中这二种癌基因表达的蛋白阳性率，ｐ５３为５９．４％，ＥＧＦＲ为６８．８％，ＥＧＦＲ在喉癌组织中的阳性率和强度与病理分级和临床预后显著性相关，ｐ５３在喉癌早期病例中表达的阳怀率明显增高。     

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     

survivin在喉癌和下咽癌中的表达及与p53、bcl-2蛋白表达的关系

目的:探讨survivin在喉癌和下咽癌中的表达情况及与p53、bcl-2间的相互关系.方法:采用免疫组织化学SP法榆测40例喉及下咽癌和10例声带息肉组织中survivin、p53及bcl-2的表达.结果:survivin、p53及bcl-2在喉癌及下咽癌中的阳性表达率分别为70.0%、57.5%和37.5%,而三者在声带息肉组织中均无表达(P＜0.05).survivin的表达随着病理分化程度的降低而增加,与临床分期、淋巴结转移成正相关(P＜0.05),与年龄无关;bcl-2的表达与临床分期成负相关(P＜0.05),与其他参数无关;p53的表达与各临床病理参数均无明显相关性.survivin在喉癌和下咽癌中的表达与p53的表达成正相关(P＜0.05),而与bcl-2的表达无相关性(P＞0.05).结论:survivin、p53可能参与喉癌及下咽癌的发生、发展并在其中起协同作用,但bcl-2则可能是通过不同的机制参与喉癌及下咽癌的发生.     

应用组织芯片探讨纤维连接蛋白和抑癌基因p53以及Ezrin表达与喉癌生物学行为的关系

OBJECTIVE: To evaluate the predictive role of fibronectin, p81 (Ezrin protein) and p53 gene in primary laryngeal carcinoma, it's relationship with epidemiology(smoking), histological grading, surgical treatment, TNM stage and prognosis were studied by the tissuechip technology. METHODS: The expression of fibronectin, p53 gene and p81 (Ezrin protein) on a series of 85 primary laryngeal carcinoma patients treated in our hospital between 1992 and 2000 was studied with tissuechip technology. The correlation of each score according to the intensity and percentage of labeled cells or intercellular substance with relevant clinical dada was statistically analyzed. RESULTS: Some cases were lost or boasted no tumor tissue in our tissuechip. Among the 70 cases available, 45.71% (32/70) of the specimens' basal membrane and extracellular matrix were strongly stained with fibronectin; there is statistical significance (P < 0.05) between primary tumor grading groups. Ezrin protein expressing rate is 87.3%, and the average percentage of its labeled cells is 53.68% (ranging from 0% to 100%, median is 58. 69%). There were significant difference between tumor grading groups, clinical early and late stages and 3-year survival rates (P < 0.05) after chi-square test. But no relation with smoking, gender, age and histological classes (P > 0.05). The average percentage of p53 positive cells is 21.6% (ranging from 0% to 90.3%, median is 5.85%) and 46.8% showed positive stains in our research. There was no statistical prominence in p53 protein demonstration between TNM stages, lymph node metastasis, 3-year survival rate, smoking, gender, age and histological classes (P > 0.05). CONCLUSIONS: The tissue microarray technique spent shorter time and less expense, and showed higher consistency in our essays. And the present study suggests fibronectin and p81 (Ezrin protein) could be the clinical discriminators in laryngeal carcinoma.     

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.     

Cell kinetics and apoptosis in laryngeal carcinoma patients

Cellular proliferation and apoptosis are both implicated in the process of carcinogenesis. The objective of this study was to access the prognostic significance of the expression of proliferating cell nuclear antigen (PCNA) and the apoptosis-related genes (bax, bcl-2, and p53) in laryngeal carcinoma patients. Thirty consecutive patients with stage I to IV squamous cell laryngeal carcinoma were treated in our department from 1992 to 1994. We immunohistochemically studied the expression of PCNA and bax, bcl-2, and p53 genes in their tumor specimens. Five healthy men were used as the control group. The staining results were correlated with clinicopathologic data. The PCNA protein expression was correlated with a significantly worse survival in those patients who were bax-negative (0% versus 42.86%, p = .0445). Similarly, the presence of PCNA led to an unfavorable clinical outcome in those patients who were bax-negative, bcl-2-negative, and p53-negative (0% versus 50%, p = .0278). Expression of bcl-2 protein was found to be an independent prognostic factor related to an unfavorable clinical outcome (p = .0262). The expression of bcl-2 protein appears to predict survival in laryngeal carcinoma patients. Furthermore, the combined study of proliferation markers and apoptosis-related genes helped us to identify a high-risk group of patients who may benefit from a more aggressive treatment protocol.     

Protein P53 in laryngeal cancer--no evidence of prognostic value

The aim of the study was to verify a relationship between P53 protein expression and prognosis in laryngeal cancer. P53 protein levels were studied by immunohistochemical staining of 80 primary laryngeal SCC. Forty five tumours (56.3%) had a positive staining for P53 protein. There was no correlation between P53 overexpression and disease-free survival. No prognostic significance of P53 protein expression in laryngeal cancer was found.     

Prognostic significance of p53 gene mutations in laryngeal cancer

OBJECTIVE/HYPOTHESIS: We examined whether p53 gene mutations were predictive of clinical behavior in laryngeal cancer. STUDY DESIGN: Retrospective study of 45 patients with laryngeal cancer from 1985 to 1997. METHODS: DNA was extracted from tumor tissue and subject to polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) as well as DNA sequencing. The clinical outcome was correlated to the presence or absence of a p53 mutation. RESULTS: The p53 gene was analyzed by direct DNA sequencing and was found to be mutated in 33% (15/45) of patients. The presence of a p53 mutation was associated with a significant improvement in overall survival (80% vs. 43%, P < .03) and a trend toward improved disease-free survival (87% vs. 60%, P = .08). When other prognostic factors were adjusted, multivariate analysis revealed a trend toward improvement in overall survival as well as disease-free survival. CONCLUSION: Depending on the location of a p53 mutation, the suppressive functions or clinical outcome may or may not be affected. Fifty-three percent of mutations were detected in nonconserved regions as opposed to 17% as reported in colon cancer. In colon cancer, mutations in conserved regions of the p53 gene predicted a poorer survival, whereas nonconserved gene mutations were not predictive. In our group of patients. p53 mutations predicted a better prognosis, which may be due to a large proportion of mutations that lie within nonconserved areas. The predictive power of p53 gene mutations may depend on functional loss and inactivation of highly conserved areas and must be tested in a prospective trial.