DJ-1蛋白在喉鳞状细胞癌中的表达及其与复发和转移的关系

目的 探讨喉鳞状细胞癌(简称鳞癌)中DJ-1蛋白表达水平与喉鳞癌临床病理特征的关系.方法 将1995年1月至2006年1月收治的71例喉鳞癌患者术后肿瘤组织和9例非喉癌者喉黏膜组织应用免疫组织化学法检测,分析其DJ-1蛋白表达水平与临床病理特征的关系.结果 喉鳞癌组织中DJ-1蛋白阳性表达率为85.9%(61/71),与非喉痛的喉黏膜组织55.5%(5/9)比较,差异有统计学意义(精确概率法P<0.05).分别就患者的性别、年龄、原发部位、T分期、临床分期、淋巴转移和肿瘤的病理学分级等情况进行分组比较,各组间喉鳞癌组织中DJ-1蛋白表达水平的差异均无统计学意义;DJ-1蛋白高表达患者其肿瘤复发率(53.3%)明显高于DJ-1蛋白低表达患者的复发率(26.8%;x2=5.164,P<0.05).Kaplan-Meier法和Cox回归分析发现喉鳞癌患者的肿瘤原发部位、性别、年龄、T分期、临床分期和肿瘤病理学分级对术后累积生存率影响均无统计学意义;DJ-1蛋白表达水平和淋巴转移对术后累积生存率影响有统计学意义(X2值分别为6.20和3.97,P值均<0.05).结论 DJ-1蛋白在喉鳞癌组织的表达水平高于喉黏膜组织.DJ-1蛋白表达水平较高的喉癌患者生存率可能低.     

Hyponatremia associated with laryngeal squamous cell carcinoma

An association between laryngeal squamous cell carcinoma and inappropriate antidiuresis is described in a 76-year-old man. Even though all accepted diagnostic criteria for the syndrome of inappropriate secretion of antidiuretic hormone were fulfilled, abnormal levels of antidiuretic hormone were not demonstrated, leaving the mechanisms of this hyponatremia unclear.     

端粒酶与喉癌相关性研究进展

端粒酶激活与恶性肿瘤发生发展之间存在着密切的关系。本文就端粒酶结构、功能及其与喉癌发生发展关系的最新研究进展作简要综述。     

程序性细胞死亡因子4在喉鳞状细胞癌中的表达及其与肿瘤细胞增殖和凋亡的关系

目的:探讨喉鳞状细胞癌中程序性细胞死亡因子4(PDCD4)蛋白表达与肿瘤细胞增殖和凋亡的关系及其临床意义。方法:采用免疫组织化学技术检测60例喉鳞状细胞癌组织及21例正常喉黏膜上皮组织中PDCD4和Ki-67的表达,原位末端标记(TUNEL)法检测细胞凋亡,以细胞增殖指数(PI)和细胞凋亡指数(AI)表示增殖与凋亡。结果:喉鳞状细胞癌组织中PDCD4蛋白阳性表达率低于癌旁正常喉黏膜组织(P<0.01),喉鳞状细胞癌组织中PDCD4蛋白阳性表达和喉鳞状细胞癌临床分型(肿瘤部位)、TNM分期无关,与病理分级、淋巴结转移有关(P<0.05);喉鳞状细胞癌组织细胞PI明显高于癌旁正常喉黏膜组织(P<0.01),细胞PI与喉鳞状细胞癌临床分型(肿瘤部位)、病理分级、淋巴结转移无关,与TNM分期有关(P<0.05);喉鳞状细胞癌组织细胞AI明显高于癌旁正常喉黏膜组织(P<0.01),细胞AI与喉鳞状细胞癌临床分型(肿瘤部位)、TNM分期、淋巴结转移无关,与病理分级有关(P<0.01);喉鳞状细胞癌PDCD4阳性表达的细胞PI低于阴性组(P<0.05),细胞AI高于阴性组(P<0.05)。结论:PDCD4在喉鳞状细胞癌中低表达,可能与喉鳞状细胞癌细胞的增殖和凋亡均有一定的关联。     

水通道蛋白1和血管内皮生长因子在喉鳞状细胞癌组织中的表达及相关性研究

目的：探讨水通道蛋白1（AQP1）和血管内皮生长因子（VEGF）在喉鳞状细胞癌（LSCC）组织中的表达及生物学意义,并探讨其相关性。方法：采用免疫组织化学方法对60例LSCC（喉癌组）、22例声带息肉组织（声带息肉组）及30例正常喉组织（对照组）中AQP1和VEGF的表达进行检测。结果：AQP1和VEGF在喉癌组的表达高于声带息肉组及对照组,3组之间差异有统计学意义;AQP1和VEGF的表达与LSCC的临床分期、病理分级以及淋巴结转移均相关,二者的表达随临床分期的增高而逐渐升高;组织分化程度越差,二者的表达越高;在有淋巴结转移的喉癌组织中二者的表达高于无淋巴结转移组;不同临床分型以及不同性别、年龄患者喉癌组中AQP1和VEGF的表达均差异无统计学意义;AQP1与VEGF在LSCC组织中的表达存在正相关。结论：LSCC组织中AQP1和VEGF蛋白的高表达及与LSCC临床病理参数的相关性,提示2个因子在LSCC发生、发展过程中起促进癌细胞生长、转移和血管生成的作用。     

Comorbidity measurement in patients with laryngeal squamous cell carcinoma

INTRODUCTION: The evaluation of a cancer patient can be affected by many factors. Cancer patients often have other diseases or medical conditions in addition to their cancer. These conditions are referred to as comorbidities. They can influence the treatment option, the rate of complications, the outcome, and can confound the survival analysis. OBJECTIVE: It was the aim of this study to measure comorbidities in patients with laryngeal squamous cell carcinoma. PATIENTS AND METHODS: Ninety adult patients treated for newly diagnosed laryngeal squamous cell carcinoma were studied. We measured comorbid illness applying the following validated scales: the Cumulative Illness Rating Scale (CIRS), the Kaplan-Feinstein Classification (KFC), the Charlson index, the Index of Coexistent Disease (ICED), the Adult Comorbidity Evaluation-27 (ACE-27), the Alcohol-Tobacco-Related Comorbidities Index (ATC), and the Washington University Head and Neck Comorbidity Index (WUHNCI). Survival analysis was performed using the Kaplan-Meier method (with the log-rank test value being used to compare groups). The Cox proportional hazards model was chosen to identify independent prognostic factors. RESULTS: The mean age was 62.3 years. The majority of patients (36.7%) had early tumors. Forty patients were treated by surgery only, while the remaining 49 patients also received postoperative radiation therapy. Only 5 patients (5.6%) were lost to follow-up. Median follow-up time was 42.5 months. The 4-year overall survival was 63%. There was a statistically significant difference between survival rates according to clinical stage (CS I 87.3%, CS II 48.9%, CS III 74.7%, CS IV 23.9%; p < 0.001). Patients treated by surgery only presented a better survival rate (79.6%) than those receiving postoperative radiation therapy (48.9%; p = 0.001). A statistically significant difference in survival rates was also noted when patients were analyzed according to the type of surgical procedure. In a univariate analysis, comorbidity had impact on prognosis, no matter which scale was utilized: CIRS (p = 0.008), ACE-27 (p = 0.010), ATC (p = 0.004), WUHNCI (p = 0.003), Charlson index (p = 0.020), KFC (p = 0.001), and ICED (p = 0.010). However, in the multivariate analysis, only CIRS and TNM staging were identified as independent prognostic factors. CONCLUSION: The comorbidity is an independent prognostic factor in patients with surgically treated laryngeal cancer. In the univariate analysis, all indexes were able to stratify patients. However, in the multiple analysis, only the CIRS was predictive of death. Comorbidities are an important factor in the analysis of overall survival.     

Proteomic signatures in laryngeal squamous cell carcinoma

Laryngeal cancer remains a worldwide health problem. The identification of biomarkers unique to laryngeal cancer may provide new insights into its pathogenesis, as well as provide potential targets for novel therapies and early detection. In order to identify potential biomarkers, we performed a proteomic analysis of laryngeal cancer specimens. Using two-dimensional differential in-gel electrophoresis and mass spectroscopy, protein expression profiles from two laryngeal carcinoma specimens and corresponding adjacent normal tissue were analyzed. The results of our analysis showed that the expression of a number of proteins was significantly altered in the tumor specimens when compared to matched normal controls. The differentially expressed proteins were identified, and they included stratifin, S100 calcium-binding protein A9, p21-ARC, stathmin, and enolase. With these findings, we have identified potential biomarkers which may contribute to the pathogenesis of laryngeal carcinoma, and which may be suitable as targets for novel therapeutic and/or diagnostic modalities.     

EphA2与VEGF蛋白在喉鳞癌组织中的表达及相关性研究

目的探讨沉默促红细胞生成素产生肝细胞受体(erythropoietin-producing hepatocellular re-ceptor,EphA2)与促血管生成因子(VEGF)蛋白在喉鳞状细胞癌(喉鳞癌)组织中的表达及相关性。方法采用免疫组织化学技术检测EphA2、VEGF蛋白在69例喉鳞癌组织及15例癌旁黏膜组织中的表达,分析二者表达水平与临床病理特征的关系。结果 EphA2和VEGF蛋白在喉鳞癌组织中的阳性率均高于癌旁黏膜组织(P均<0.05),EphA2蛋白表达尚与肿瘤原发部位相关(P<0.05),且EphA2和VEGF蛋白表达均与喉鳞癌患者的临床分期(P均<0.05)及转移(P均<0.05)密切相关,而二者表达与患者年龄、性别、组织学分级均无明显相关(P均>0.05)。喉鳞癌组织中EphA2及VEGF蛋白表达存在正相关性(P<0.05)。生存分析结果显示EphA2及VEGF蛋白表达水平与患者5年总生存率密切相关(P<0.05)。多因素Cox比例风险回归模型进一步显示,淋巴结有无转移及EphA2蛋白表达水平为喉鳞癌患者预后的独立影响因素。结论 EphA2与VEGF蛋白在喉鳞癌组织中表达均上调,提示二者可能存在相互作用,共同在喉鳞癌的发生、发展中起作用。     

真核细胞翻译起始因子4E和血管内皮生长因子在喉鳞状细胞癌中的表达及相关性研究

目的：通过检测真核细胞翻译起始因子4E(eIF4E)与血管内皮生长因子(VEGF)在喉鳞状细胞癌(LSCC)中的表达,探讨二者与LSCC的关系及其相互之间的内在联系。方法：采用Western-blot法检测20例新鲜LSCC标本的癌中心区(TC)、过渡区(TR)及病理证实的无癌区(TF)中eIF4E及VEGF的表达情况。结果：eIF4E在LSCC的TF、TR及TC的表达水平呈递进性增高;VEGF在LSCC的TC的表达水平显著高于TR及TF;eIF4E与VEGF二者密切相关。结论：过表达的eIF4E是LSCC恶性改变及判断其恶性程度的一个分子标志;VEGF的高表达与LSCC的生长及转移密切相关,其或许可以作为判断预后的指标之一。二者在LSCC中的表达具有相关性,可为LSCC的基因治疗提供一定的理论基础。     

HMGB1与VEGF蛋白在喉鳞状细胞癌中的表达及其相关性研究

目的:检测高迁移率族蛋白1(HMGB1)、血管内皮生长因子(VEGF)蛋白在喉鳞状细胞癌(LSCC)组织中的表达及其生物学意义,并探讨二者之间的相关性.方法:采用免疫组织化学技术检测HMGB1、VEGF蛋白在69例LSCC及15例癌旁黏膜组织中的表达,统计分析二者表达水平与临床病理特征的关系.结果:HMGB1和VEGF蛋白在喉癌组织中的阳性表达率均高于对照组(均P<0.05),且HMGB1蛋白和VEGF蛋白表达均与LSCC的临床分期(P<0.05)及转移(P<0.05)密切相关,而二者表达与患者年龄、性别、组织学分级、肿瘤原发部位无明显相关(均P>0.05).喉癌组织中HMGB1及VEGF蛋白表达存在正相关性(P<0.05).Kaplan-Meier生存分析结果显示HMGB1及VEGF蛋白表达水平与患者5年总生存率密切相关(均P<0.05).COX比例风险回归模型进一步显示,淋巴结有无转移及HMGB1表达水平为LSCC患者预后的独立影响因素.结论:LSCC组织中HMGB1与VEGF蛋白的表达与临床分期、淋巴结转移及预后密切相关;该两基因在LSCC组织中表达上调,提示该两基因可能在喉癌的发生、发展中起重要作用.     

Variability of the thymidine labeling index in squamous cell carcinoma of the head and neck

Tritiated thymidine (³HTdR) labeling is the standard technique for determining the kinetic activity of tumors. This method has been used to label multiple sections of tumor specimens obtained from seven patients with advanced squamous cell carcinoma of the head and neck. Considerable variability was observed in the labeling index in different sites from the same specimen. To reduce the large sampling error due to heterogeneity, we recommend that an average value be determined from multiple sections when employing this technique.     

细胞周期蛋白D1基因的表达与喉鳞癌相关性研究

目的：探讨细胞周期蛋白Ｄ１的表达与喉鳞癌（ＳＣＣＬ）的关系。方法：对３５例经病理证实ＳＣＣＬ患者的肿瘤组织及其邻近的正常粘膜,运用反转录多聚酶链反应（ＲＴ－ＰＣＲ）、光密度半定量法,分别检测其ｃｙｃｌｉｎ Ｄ１的表达程度。结果：发现几乎所有的肿瘤标本的表达量要高于正常粘膜（Ｐ〈０．０５）,有淋巴结转移者的表达量要明显高于无淋巴结转移者（Ｐ〈０．０５）;表达量与ＴＭＮ分期也有明显的相关性（Ｐ〈０．０     

Survivin在喉鳞状细胞癌、喉乳头状瘤及喉黏膜白斑中的表达及意义

目的 探讨Survivin蛋白在喉鳞状细胞癌、喉乳头状瘤及喉黏膜白斑中的表达及其意义。方法 应用免疫组化对46例喉鳞状细胞癌、24例癌旁组织、20例喉乳头状瘤、28例喉黏膜白斑和16例正常喉黏膜中Survivin的表达情况进行检测。结果 Survivin蛋白在喉癌组织和癌旁组织、喉黏膜白斑及喉乳头状瘤中的阳性表达率分别为71．74％（33／46）、33．33％（8／24）、46．43％（13／28）；40％（8／20），在正常黏膜组织中无表达。喉癌组中的阳性表达率显著高于癌旁组织、喉黏膜白斑、喉乳头状瘤及正常黏膜组织中的表达率。且喉乳头状瘤组及喉黏膜白斑组中发生恶变的组织中Survivin蛋白均为阳性表达。Survivin蛋白的阳性表达与喉癌的发生部位、分级、分期、淋巴结转移以及病理分级无关。结论 Survivin在喉癌组织中过度表达参与了喉癌的形成，对喉癌的癌前病变发展成恶性肿瘤的潜在可能性有预测作用。     

基质金属蛋白酶MMP20与喉癌的浸润和转移

目的探讨基质金属蛋白酶MMP20与喉癌浸润和转移的关系.方法用RT-PCR和免疫组化的方法,研究MMP20在喉癌组织和其相邻的正常黏膜组织的差异表达量,分析其表达与喉癌浸润和转移的关系.数据分析借助SPSS10.0软件完成.结果 36例配对标本中MMP20基因在31例喉癌组织中的表达与其相应的正常黏膜组织差异表达不明显,而在5例喉癌组织中差异表达明显;MMP20蛋白绝大多数在癌巢细胞浆内表达（占93.2%,68/73）,少数主要在细胞核内表达（占6.8%,5/73）,MMP20蛋白在大多数喉癌组织中的表达明显高于其相应的正常黏膜组织;有淋巴结转移病例中,MMP20蛋白表达差异明显的病例数高于没有淋巴结转移者（P=0.023）;5例MMP20蛋白喉癌组织细胞核内表达中有4例与淋巴结转移有关.结论 MMP20蛋白在喉癌的淋巴结转移中起着重要的作用;MMP20蛋白的过度表达可作为喉癌淋巴结转移的标志.     

MIF、GSK-3β在喉鳞状细胞癌中表达的临床意义及相关性研究

目的 探讨巨噬细胞移动抑制因子(MIF)及糖原合成激酶-3(GSK-3β)在喉鳞状细胞癌中表达的临床意义及相关性。 方法 采用免疫组化法检验30例喉癌患者癌组织及相应癌旁组织中MIF、GSK-3β的表达情况,并以10例非喉鳞状细胞癌患者喉部正常黏膜组织作对照;分析喉组织中MIF、GSK-3β表达与患者临床病理因素之间的关系,探讨喉鳞状细胞癌中MIF与GSK-3β表达的相关性。 结果 喉癌组织中、癌旁组织及喉正常喉黏膜中MIF表达率分别为73.33%,40.00%,20.00%,喉癌组织中、癌旁组织及喉正常喉黏膜中GSK-3β阳性表达率分别为70.00%,13.33%,20.00%;MIF、GSK-3β在喉癌中表达与肿瘤分化程度、TNM分期及淋巴结转移均相关(P<0.05);与患者年龄、性别、吸烟史和饮酒史均无相关性(P>0.05)。MIF、GSK-3β在喉癌中的表达具有相关性(r=0.592,P=0.003)。 结论 喉鳞状细胞癌中MIF、GSK-3β的高表达可促进喉癌的发生及发展,MIF、GSK-3β可作为喉癌的潜在的组织生物标志物和喉癌患者疾病进展监控及预后观测的指标。     

Laser Doppler flux-metry in laryngeal squamous cell carcinoma

Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Novel antiangiogenic therapy for solid tumours including laryngeal cancer is entering clinical trials. Quantifying microvessel density is considered the gold standard for measuring baseline angiogenesis and indeed 'the response to intervention'. We hypothesize that laser Doppler flux-metry could provide a non-invasive reliable method of quantifying blood flux within tumours. The aims were to determine whether a laser Doppler flux meter could be used as a reliable and reproducible method of estimating blood flux in the human larynx and to establish baseline Doppler flux recordings for the human larynx. The method used was a validation study in patients with laryngeal squamous cell cancer and normal controls. Statistical analysis was performed using SPSS software. We have demonstrated good reproducibility of laser Doppler measurements in human laryngeal mucosa (correlation coefficient 0.956 @P = 0.01). We have also derived arbitrary means of laser Doppler flux-metry in normal laryngeal mucosa and in squamous cell carcinoma of the larynx. Comparisons between normal and tumour laser Doppler flux-metry (LDF) readings showed no significant difference. We suggest that Laser Doppler flux-metry is a potentially useful tool with which to study blood flow in the larynx and propose arbitrary LDF levels for the normal and diseased human larynx.     

Eosinophilic infiltration in advanced laryngeal squamous cell carcinoma

Tumor-associated tissue eosinophilia (TATE) has been related to prognosis in epithelial cancers, including cancers at several head and neck sites. This study prospectively examined 248 patients with stage in and IV laryngeal squamous cell carcinoma to determine prevalence and potential prognostic significance of TATE. Pretreatment tumor specimens were histopathologically evaluated. Presence and degree of TATE were analyzed with regard to other tumor characteristics, patient characteristics, and outcome criteria. Median follow-up was 48 months. Eosinophilia was found in 22.5% of specimens and was not related to tumor site, stage, patient age or sex, or treatment modality. Overall and disease-free survival rates and response to induction chemotherapy did not differ significantly with respect to TATE. This study represents the first long-term, prospective evaluation of TATE and its prognostic significance in a single head and neck site. Contrary to the findings of earlier preliminary reports, our results suggest that TATE is not a clinical useful prognostic parameter in advanced laryngeal squamous cell carcinoma.