口腔鳞状细胞癌中血管内皮生长因子-C的表达及其与血管、淋巴管生成、淋巴结转移的关系

目的探讨血管内皮生长因子-C（VEGF-C）在口腔鳞状细胞癌（OSCC）组织中的表达情况及其与血管、淋巴管生成、淋巴结转移之间的关系。方法调查拥有完整临床病理资料的67例口腔鳞癌患者的手术切除标本,采用SP免疫组化技术检测VEGF-C的表达情况并分析其与微血管密度（MVD）、淋巴管密度（LVD）及其他临床病理指标的关系。结果晚期病例、淋巴结转移阳性病例的VEGF-C表达明显升高（P值分别为0.015和<0.001）,而VEGF-C表达与患者性别、肿瘤部位、肿瘤分化程度无关（P>0.05）。VEGF-C高表达组的LVD明显高于VEGF-C低表达组（P=0.001）,但两组间MVD无统计学差异（P=0.125）。此外,淋巴结转移阳性组的LVD明显高于淋巴结转移阴性组（P=0.026）。结论VEGF-C可能主要通过参与诱导口腔鳞癌淋巴管生成促进淋巴结转移。     

口腔鳞癌中VEGF-C的表达及与颈淋巴转移的关系

目的：检测口腔鳞癌（OSCC）中血管内皮生长因子-C（VEGF-C）的表达,以探讨VEGF-C与OSCC淋巴转移的关系及其临床意义。方法：应用免疫组织化学染色（S-P法）检测40例OSCC组织及14例正常口腔黏膜组织中VEGF-C的表达情况。结果：45.0%的OSCC组织中可见VEGF-C表达,在正常口腔黏膜中无表达;22例伴淋巴结转移的OSCC组织中,68.2%有VEGF-C表达,18例不伴有淋巴结转移者,16.7%有VEGF-C表达,两组之间差异有统计学意义（P〈0.01）;16.7%的Ⅰ～Ⅱ期OSCC有VEGF-C表达,57.1%的Ⅲ～Ⅳ期OSCC有VEGF-C表达,两者之间差异有统计学意义（P〈0.05）;与肿瘤的部位、年龄及性别无关（P〉0.05）。结论：VEGF-C在OSCC组织中表达明显上调,并与淋巴管生成、颈淋巴结转移及TNM分期等临床病理生物学行为有关,提示VEGF-C可能在OSCC的生长及转移中起重要作用。     

舌鳞状细胞癌淋巴管密度与淋巴转移的关系

目的 探讨舌鳞癌组织中淋巴管密度与鳞癌侵袭和转移的关系.方法 选择62例舌鳞癌标本,采用免疫组化SP法检测血管内皮生长因子受体-3(VEGFR-3)和血管内皮生长因子-D(VEGF-D)的表达.结果 62例舌鳞癌标本中有56例标本的VEGFR-3呈阳性表达,但功能性淋巴管主要分布在癌组织周围,癌间质中未见明显的成形淋巴管.舌鳞癌组织中淋巴管密度与舌鳞癌患者年龄、性别无关,而与舌鳞癌病理分级、临床分期和有无淋巴结状况密切相关(P＜0.05).VEGF-D在癌细胞胞质呈阳性表达,且随着VEGF-D表达增强,癌组织周围淋巴管密度亦明显增加.结论 VEGF-D和VEGFR-3途径可促进鳞癌淋巴管新生和淋巴转移.     

血管内皮生长因子-C在不同浸润方式的舌鳞状细胞癌中的表达

目的 探讨血管内皮生长因子(VEGF)-C在不同浸润方式的舌鳞状细胞癌中的表达差异.方法 参照Anneroth等描述的肿瘤浸润方式对39例舌鳞状细胞癌进行分型,免疫组织化学染色观察VEGF-C的表达情况.结果 在不同浸润方式的舌鳞状细胞痛,VEGF-C的表达不同.在Ⅲ、Ⅳ型的舌鳞状细胞癌,VEGF-C的表达明显高于Ⅰ、...     

Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in oral squamous cell carcinoma: its correlation with angiogenesis and disease progression

BACKGROUND: Angiogenesis is a crucial step in the successful growth, invasion, and metastasis of a tumor. It has been popularly accepted that vascular endothelial growth factor (VEGF) is the most potent angiogenic factor in tumor angiogenesis. As another possible star molecule responsible for tumor angiogenesis, the role of nitric oxide (NO) in tumor biology has gained much attention in recent years. The aim of this study was to investigate whether the expression of endothelial nitric oxide synthase (eNOS) and VEGF in oral squamous cell carcinoma (OSCC) is associated with angiogenesis. The present study also made a preliminary exploration of the possible cross-talking existing between eNOS and VEGF during tumor angiogenesis. METHODS: In this study, expression of eNOS and VEGF were studied immunohistochemically in tissue sections from 40 patients with OSCC and 20 normal controls. To exclude eNOS antibody cross-reactivity with inducible or neuronal nitric oxide (iNOS or nNOS), eNOS expression was confirmed by using an eNOS mRNA in situ hybridization kit. The intratumoral microvessels were highlighted by immunostaining with anti-factor VIII-related antigen monoclonal antibody and counted as well-established methods. Then, chi-square test or Student's t-test was performed to study the correlations between the expression of eNOS and VEGF, microvessel density (MVD), and various clinicopathologic factors. RESULTS: Both eNOS and VEGF expression significantly increased in OSCC tissues, with a positive rate of 47.5% and 50%, respectively. The average MVD in OSCC tissues was 23.45 per high-power field (HPF), showing an obvious association with lymph node metastasis and clinical stages of patients with OSCC. Either eNOS or VEGF positivity was correlated with vessel involvement and OSCC progression. The mean MVD was significantly higher in eNOS- or VEGF-positive tumors than in eNOS- or VEGF-negative tumors. An obvious, correlation was also seen between eNOS and VEGF expression in OSCC tissues in this study. CONCLUSIONS: Overexpression of eNOS and VEGF might make an important contribution to the tumor angiogenesis in OSCC. NO generation by eNOS might be implicated in the VEGF-associated angiogenic process. Further investigation of the possible cross-talking between eNOS and VEGF with respect to tumor angiogenesis is necessary.     

口腔鳞状细胞癌血管内皮细胞生长因子的表达

目的 :研究口腔鳞癌血管内皮细胞生长因子 (VEGF)和血管生成的关系 ,并评价VEGF、微血管密度(MVD)的临床意义。方法 :采用免疫组化SP法 ,用CD3 4 单抗标记血管内皮细胞 ,VEGF多抗标记VEGF蛋白 ,检测了 45例口腔鳞癌的VEGF表达和血管生成情况。结果 :①VEGF主要在胞浆表达 ,血管生成在癌巢周边的间质内 ;②VEGF阳性者MVD明显增高 ;③高MVD和VEGF阳性者的患者颈淋巴结转移的机率明显增高 ;④高MVD和VEGF高表达的患者 5年生存率明显降低。结论 :①口腔鳞癌组织表达VEGF ,它参与促进肿瘤的微血管形成 ;②口腔鳞癌的MVD和VEGF对颈淋巴结转移有较高的预测价值 ;③MVD和VEGF可以指示患者的预后情况     

胸苷磷酸化酶与口腔鳞癌血管新生及预后的关系

目的：探讨胸苷磷酸化酶（TP）与口腔鳞癌（OSCC）临床病理及预后的关系,并研究其与微血管密度（microvessel density,MVD）的相关性。方法：用SP免疫组化法检测63例OSCC中TP的表达水平,利用CD34标记的血管进行MVD计数,对所有病例进行随访。采用SPSS13.0软件包进行统计学分析,以χ2检验分析TP的表达及其与各临床病理因素及MVD间的关系,应用寿命表法完成对病例随访资料的生存状况评价。结果：TP在口腔鳞癌组织中的表达显著高于正常口腔黏膜组织（P〈0.01）;TP的表达与肿瘤的颈淋巴结转移密切相关（P〈0.01）,而与患者性别、年龄、临床分期及病理分化程度无明显相关（P〉0.05）;TP表达阳性组的MVD高于TP表达阴性组（P〈0.05）;TP的表达与MVD呈正相关（P〈0.05）。生存分析显示,TP阴性组的5年生存率高于TP阳性组,术后复发组的TP表达阳性率（90.9%）显著高于术后无复发者（50.0%）（P〈0.05）。结论：TP的表达水平与口腔鳞癌的颈淋巴结转移、血管新生及预后密切相关,可以作为其一项不良因子。     

口腔癌细胞诱导的淋巴管内皮细胞基因表达谱的变化

目的探讨在口腔癌细胞影响下淋巴管内皮细胞分子表型的变化。方法利用体外共培养模型,将淋巴管内皮细胞与口腔癌细胞进行共培养,模拟肿瘤中淋巴管内皮细胞的变化。应用Affymetrix U133 Plus 2.0基因芯片对肿瘤组织中淋巴管内皮细胞（TLEC）与淋巴管内皮细胞（LEC）基因表达的差异进行了检测和比较。并对功能相似的表达差异基因进行分类。结果差异基因表达谱共发现了677个基因表达差异在1倍以上,其中在TLEC中表达上调的基因有384条,下调的基因有293条。这些基因与细胞黏附、凋亡、运动、发育及血管生成有关。同时这些基因还参与细胞的信号传导、免疫应答、细胞代谢等过程。结论LEC与TLEC在分子水平是有差别的。以此为基础,可以针对淋巴管内皮细胞进行靶向阻断,达到治疗口腔癌淋巴道转移的目的。     

microRNA表达调控与口腔鳞状细胞癌

［摘要］ 微小RNA(microRNA,miRNA)属于一类小非编码RNA,可以通过作用于目标信使RNA(messenger RNA, mRNA)来调控生物进程。miRNA具有作为肿瘤生物标志物和药物作用靶点的潜能,因此阐明其在肿瘤发生发展中的作用机制十分重要。口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)是一种常见的口腔恶性肿瘤,预后不良。该文对miRNA在OSCC中的生物学功能,相关表达谱改变,调控机制和临床应用前景作一综述。     

口腔鳞癌中COX-2、VEGF-C的表达及其临床意义

目的：检测口腔鳞癌（OSCC）中COX-2、VEGF-C的表达,以探讨COX-2、VEGF-C与OSCC淋巴转移的关系及其临床意义。方法：应用免疫组织化学染色S-P法检测COX-2、VEGF-C在OSCC中的表达情况。结果：COX-2在OSCC组织中表达明显高于正常口腔黏膜（P〈0.01）;COX-2在伴淋巴结转移者的阳性表达率明显高于不伴淋巴结转移者（P〈0.05）。VEGF-C在OSCC组织中表达明显高于正常口腔黏膜（P〈0.01）;VEGF-C在伴淋巴结转移者的阳性表达率明显高于不伴淋巴结转移者（P〈0.05）。40例OSCC组织中,COX-2与VEGF-C表达共阳性16例（40.0%）,表达阴性10例（25.0%）,二者在OSCC中的表达成正相关（r=0.517,P〈0.01）。结论：COX-2、VEGF-C在OSCC组织中表达明显上调,并与淋巴结转移有关,提示二者有可能在OSCC的生长及转移中起重要作用。COX-2表达上调与VEGF-C表达成正相关,提示二者在OSCC的淋巴管生成及侵袭转移中可能起协同作用。     

The prevalence of oral leukoplakia in 138 patients with oral squamous cell carcinoma

OBJECTIVES: To determine the relationship between oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), and to evaluate possible differences between those carcinomas with and without associated leukoplakia. MATERIAL AND METHODS: A total of 138 patients were studied at the Stomatology Service of the University General Hospital, Valencia, Spain. These patients were divided into two groups: group 1, patients with oral cancer and leukoplakia, and group 2, patients with OSCC but with no associated premalignant lesions. The relationship between this precancerous lesion and the OSCC was evaluated, as well as the possible clinical and histological differences between the tumours of the two groups. RESULTS: Leukoplakia was detected in 27 (19.56%) patients with OSCC. No differences were found between the two groups regarding age and tumour location. However, statistically significant differences were observed with respect to the form, tumour stage and the presence of adenopathies in the cancers with and without leukoplakia; in that the tumours associated with leukoplakia were diagnosed as being at a more initial stage. CONCLUSIONS: Those patients with OL associated with oral cancer presented with tumours at a less advanced stage than those where no associated leukoplakia existed.     

亲环蛋白A与口腔恶性肿瘤间的关系

亲环蛋白A是一类在生物界广泛存在、高度保守的蛋白质,有多种生物学功能并参与多种生理病理过程.下面就其在肿瘤尤其是在口腔鳞状细胞癌的发生、侵袭、增殖、血管生长等过程中的作用作一综述.     

血管细胞黏附分子-1在口腔鳞状细胞癌中的表达及其意义

目的研究血管细胞黏附分子-1（VCAM-1）在口腔鳞状细胞癌（OSCC）中的表达与定位及其临床意义。方法应用分子原位杂交和免疫组化方法对48例OSCC组织和10例正常口腔黏膜组织中VCAM-1 mRNA和VCAM-1蛋白质的表达和定位进行检测,比较VCAM-1在不同口腔组织中的表达率及其与临床指标的关系。结果VCAM-1蛋白定位于肿瘤细胞胞浆和胞膜,VCAM-1 mRNA定位于肿瘤细胞胞浆。VCAM-1 mRNA和VCAM-1蛋白在OSCC中的表达率均显著高于正常口腔黏膜组织（P＜0.01）,VCAM-1 mRNA表达与VCAM-1蛋白表达呈正相关（P＜0.01）;OSCC中淋巴结转移者VCAM-1蛋白的表达显著高于无淋巴结转移者（P＜0.01）。结论OSCC中VCAM-1基因的高表达可能与肿瘤的浸润和转移有关。     

EP—CAM在OLP和OSCC组织中的表达及意义

目的：观察上皮细胞黏附分子（Ep—CAM）在口腔正常黏膜、扁平苔癣（OLP）和鳞癌（OSCC）组织中表达的变化,分析Ep—CAM在口腔黏膜疾病及其癌变发病机制中的作用。方法：采用免疫组织化学法检测10例正常口腔黏膜、30例OLP（15例非糜烂型、15例糜烂型）及20例OSCC组织中Ep—CAM的表达变化。结果：Ep—CAM在正常黏膜组织阴性表达,而在非糜烂型OLP、糜烂型OLP及OSCC组织中表达逐渐增强。结论：Ep—CAM在口腔黏膜癌变的发展过程中可能具有一定的指示意义。     

Prognostic significance of extranodal extension in oral cavity squamous cell carcinoma with occult neck metastases

A grade of extranodal extension (ENE) may advance risk stratification related to survival in patients with metastatic oral cavity squamous cell carcinoma (OCSCC). Pathological examination of 174 OCSCC patients who were primarily surgically treated with tumour resection and elective neck dissection was performed. Data of ENE presence, its extent (in millimetres), patients and tumour characteristics were statistically analysed with respect to disease-free survival (DFS) and overall survival (OS). Ninety patients (51.7%) were identified with occult nodal disease, with 41 patients (23.6%) presenting with ENE. Receiver operating characteristics (ROC) curve analysis set the threshold at 1.9 mm as an optimal ENE cut-off regarding both DFS and OS. Patients were divided by extent into minor ENE (≤1.9 mm) and major ENE (>1.9 mm) subgroups. The subgroup with minor ENE had significantly higher DFS and OS rates compared with major ENE. ENE cut-off threshold at 1.9 mm discriminates low and high-risk subgroups of patients with occult OCSCC in terms of DFS and OS.     

血管内皮生长因子在口腔扁平苔藓及鳞癌组织中的表达

目的探讨血管内皮生长因子在口腔扁平苔藓癌变及发病机制中的作用。方法采用免疫组化法,检测10例正常口腔黏膜、25例口腔扁平苔藓、11例口腔扁平苔藓伴不典型增生及14例口腔鳞癌,上皮组织中血管内皮生长因子的表达水平。结果血管内皮生长因子在24例口腔扁平苔藓标本中阳性表达2例,阴性表达22例,阳性表达率明显低于其它3组（P〈0.05）。扁平苔藓伴不典型增生及口腔鳞癌中血管内皮生长因子的阳性表达率均高于正常黏膜（P〈0.05）。结论血管内皮生长因子的表达异常可能在口腔扁平苔藓的发生发展及癌变的过程中起作用。