鼻咽癌微血管与远处转移关系的初步研究

目的 研究肿瘤血管参数改变在鼻咽癌远处转移中的及其评价预后的作用；并由此探讨抗篾这生成治疗预防鼻咽癌远处转移的可能性。方法 选择５２例初治转移鼻咽癌，与另５２例初治无转移且长期无瘤生存的鼻咽癌在性别、年龄、Ｔ分期和Ｎ分期方面进行一对一配对，取其组织进行微血管的免疫组化染色和计算机图象分析，配对比较４个参数；微血管计数、微血管相对面积、平均血管面积和平均血管周长。并分析这些参数在各型转移鼻咽癌中的差     

鼻咽癌的血管生成及其临床意义

目的　探讨血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)的表达和微血管密度 (mi crouesseldensity ,MVD)在鼻咽癌中的临床意义。方法　采用免疫组织化学S -P法 ,研究 4 0例鼻咽癌组织和10例正常鼻咽黏膜组织切片中的血管内皮生长因子的表达和微血管密度。结果　血管内皮生长因子主要定位于肿瘤细胞的胞浆和胞膜 ,鼻咽癌组织中血管内皮生长因子的表达阳性率为 92 .5 % (37/ 4 0 ) ,明显高于正常鼻咽黏膜组织 (P <0 .0 5 ) ,微血管密度也明显高于正常鼻咽黏膜组织 (P <0 .0 5 ) ,且二者具有相关性 (相关系数为 0 .80 9,P <0 .0 5 ) ,并与鼻咽癌病人分期、淋巴结转移和骨、肺、肝等远处转移有关。结论　鼻咽癌血管内皮生长因子的表达和微血管密度与肿瘤淋巴结转移和远处转移有关 ,血管生成在鼻咽癌生长、浸润、转移中起着重要的作用。血管内皮生长因子的表达和微血管密度可以作为鼻咽癌病人有意义的预后指标。     

鼻咽癌血管生成及血小板聚集功能与侵袭转移关系的研究

目的：探讨鼻咽癌（ＮＰＣ） 血管生成及血小板聚集功能与ＮＰＣ 侵袭转移关系,为在分子水平干预肿瘤血管形成,预防ＮＰＣ复发和转移打下基础。方法：采用免疫组织化学Ｓ－ Ｐ法检测了５６ 例ＮＰＣ,２０ 例无瘤鼻咽部石蜡标本组织中的微血管密度（ ＭＶＤ） 及血管内皮细胞生长因子（ＶＥＧＦ） 表达。随访３ 年,ＮＰＣ复发转移１７ 例,无复发或转移３９ 例。结果：复发转移组的血小板聚集率ＭＡＲ,ＭＶＤ 及ＶＥＧＦ的表达较无复发转移的表达高,差异有统计学意义;ＭＶＤ 及ＶＥＧＦ的表达与临床分期相关。结论：ＮＰＣ 血管生成及血小板聚集功能亢进与癌浸润和转移行为密切相关,有可能作为判断肿瘤生物学行为及预后指标,对采用血管生成抑制剂及血小板聚集抑制剂防止ＮＰＣ转移有参考价值。     

鼻咽癌患者血管内皮生长因子与微血管密度的检测及临床意义

目的:探讨血管内皮生长因子(VEGF)在鼻咽癌肿瘤组织血管生成中的作用。方法:用酶联免疫吸附实验(ELISA)检测62例初诊鼻咽癌患者和20例鼻咽部炎症患者血清和组织中VEGF蛋白水平,SP法检测鼻咽癌和鼻咽部炎症患者组织中微血管密度(MVD)。结果:①鼻咽癌VEGF及MVD水平与患者年龄、性别无明显相关,但晚期组(Ⅲ+Ⅳ)鼻咽癌显著高于早期组(Ⅰ+Ⅱ)患者(P<0.01),有淋巴结或远处转移组高于无淋巴结或远处转移组(P<0.01);②鼻咽癌组织及外周血中VEGF表达均高于鼻咽炎组(P<0.05),同样鼻咽癌组织MVD显著高于鼻咽炎组(P<0.01);③鼻咽癌组织中VEGF表达与MVD呈显著正相关(r=0.865,P<0.01),而鼻咽癌外周血VEGF与MVD无相关性(r=0.328,P>0.05)。结论:VEGF诱导鼻咽癌肿瘤局部血管生成,促使疾病进展,可能成为评价鼻咽癌预后的一个重要指标。     

鼻咽癌淋巴管和微血管同期检测与预后

目的:观察微血管和淋巴管密度在鼻咽癌中的分布特点,探讨其对鼻咽癌复发转移和预后的意义。方法:对106例鼻咽癌患者的组织标本,采用微血管和淋巴管特异性标记物CD34和D2-40同期进行免疫组化检测,通过计算机辅助图像分析系统定量分析肿瘤周边及中心区域微血管和淋巴管分布状况,跟踪随访36～45个月,分析其与鼻咽癌复发转移和预后的关系。结果:106例鼻咽癌患者组织标本中,微血管和淋巴管染色均呈阳性表达,瘤周微血管和淋巴管密度均大于瘤内。单因素分析显示瘤内微血管密度、瘤内和瘤周淋巴管密度与鼻咽癌复发转移相关(P<0.05),而年龄、性别、T分期、N分期、临床分期,以及瘤周微血管密度与之不相关(P>0.05);多因素分析显示瘤内微血管密度和瘤周淋巴管密度是鼻咽癌复发转移的独立风险因素。瘤内微血管密度高表达与鼻咽癌的不良预后密切相关(P<0.05)。结论:微血管和淋巴管密度高表达是评估鼻咽癌预后不良的指标。瘤内和瘤周微血管、淋巴管在肿瘤复发转移中可能发挥着不同的作用,瘤内微血管和癌周淋巴管应成为鼻咽癌治疗的靶点。     

鼻咽癌预后的新指标-肿瘤血管生成和c-erbB2表达

鼻咽癌局部生长和远处转移快，放射治疗敏感，预后较差。本文对２５２例连续治疗的鼻咽癌病人进行回顾性研究，目的是探讨肿瘤血管生成、肿瘤蛋白（Ｃ－ｅｒｂＢＺ）、肿瘤基因表皮生长因子受体（ＥＧＦＲ）、细胞增生指数（Ｋｉ－６７）、肿瘤抑制基因（Ｐ。。）评价鼻咽癌远端转移和预后的价值。２５２例中，材料完整者仅有３０例，均经过基础放射治疗，平均年龄５０岁，男２１例女９例，症状期７个月，平均随访４４个月，局部复发时间平均为１１·５个月，远处转移的平均时间为３个月。对早期的活组织标本切片进行苏木精一伊红染色，光镜…     

鼻咽癌血管生成及血小板聚集功能与侵袭转移关系？…

目的：探讨鼻咽癌血管生成及血小板聚集功能与ＮＰＣ侵袭转移关系，为在分子水平干预肿瘤血管形成，预防ＮＰＣ复发和转移打下基础。方法：采用免疫组织化学Ｓ－Ｐ法检测了５６例ＮＰＣ，２０例无瘤鼻咽部石蜡标本组织中的微血管密度及血管骨皮细胞生长因子表达。随访３年，ＮＰＣ复发转移１７例，无复发或转移３９例。结果：复发转移组的血小板聚集率ＭＡＲ，ＭＶＤ及ＶＥＧＦ的表达较无复发转移的表达高，差异有统计学意义；ＭＶＤ     

鼻咽癌局部扩散与远处转移的相关性

目的:探讨鼻咽癌局部和区域扩散与远处转移的相关性。方法:分析204例鼻咽癌初治患者的临床资料(其中放疗后无瘤生存≥5年者101例,为无瘤组;放疗后远处转移者103例,为转移组),重新阅读其治疗前CT片,确定局部扩散范围和方式,并进行单因素和Cox模型分析。结果:单因素分析表明,鼻窦侵犯,颅底破坏,脑神经损害,咽旁间隙侵犯程度,颈淋巴结转移侧数、个数、大小及活动度,临床分期,T分期与N分期均具有统计学意义(均P<0.05);多因素分析只显示鼻窦侵犯,脑神经损害,颈淋巴结转移侧数、个数和大小,临床分期具有统计学意义;对局部扩散各种因素与区域扩散相关性分析显示,无论是局限性病变,还是颅底、咽旁间隙等扩散,转移组并区域淋巴结转移及其转移程度(N2,3)均明显高于无瘤组(P<0.05或P<0.01)。结论:区域淋巴结转移及其程度是鼻咽癌放疗后远处转移最主要、最恒定的因素,原发灶局部扩散主要是通过区域淋巴结转移来影响远处转移。     

血管生成拟态和内皮依赖性血管在喉癌转移中的作用研究

目的 探讨血管生成拟态和内皮依赖性血管在喉鳞状细胞癌侵袭转移过程中的作用,用以评估患者的预后.方法 回顾性分析203例喉癌患者临床病理资料及随访结果.CD31和过碘酸雪夫试剂免疫组化双重染色及CD31染色标记石蜡包埋喉癌组织中血管生成拟态及内皮依赖性血管的表达,应用Kruskal-Wallis检验和单因素方差分析比较血管生成拟态和内皮依赖性血管与喉癌患者临床病理参数的关系,并应用Kaplan-Meier进行生存分析,评估患者的预后.结果 血管生成拟态与喉癌患者的淋巴转移、肿瘤分期和组织病理学分级有关(P值均＜0.05).而内皮依赖性血管与喉癌患者的发病部位、肿瘤分期、T分期和远处转移有关(P＜0.05).单因素分析表明,血管生成拟态(P=0.014)、肿瘤分期(P=0.009)、T分期(P=0.013)、淋巴转移(P=0.013)、组织病理学分级(P=0.038)、肿瘤大小(P=0.028)和放疗(P＜0.0001)与喉癌患者总生存率有关.而血管生成拟态(P=0.011)、发病部位(P=0.049)、肿瘤大小(P=0.001)和放疗(P ＜0.0001)与喉癌患者无瘤生存率有关.多因素分析结果表明,血管生成拟态是影响喉癌患者预后的独立危险因素.结论 喉癌组织中内皮依赖性血管与血管生成拟态共存.血管生成拟态可能通过促进区域淋巴转移影响喉癌患者的生存,对预测喉癌患者的转移和生存具有重要价值.     

微血管密度与鼻咽癌生物学行为的相关性

探讨鼻咽癌血管生成与癌生物学行为的关系。方法采用免疫组织化学ＳＰ法检测了６５例ＮＰＣ、１５例鼻咽良性肿瘤、１５例无瘤者鼻咽部石蜡标本组织中的微血管密度及血管内皮细胞生长因子表达。     

The relationship between microvessel density, the expression of vascular endothelial growth factor (VEGF), and the extension of nasopharyngeal carcinoma

OBJECTIVE: The present study was aimed at clarifying whether the microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF) were related to the degree of local invasion and metastasis in nasopharyngeal carcinoma (NPC). STUDY DESIGN: We measured the MVD and examined whether VEGF was expressed in NPC tissue using histological study combined with immunohistochemistry. METHODS: MVD and VEGF expression was measured in 73 specimens of NPC, 15 benign tumors of nasopharyngeal region, and 20 nasopharyngeal tissue without tumor. MVD and VEGF expression in NPC was compared between a metastasis group (49 specimens) and a non-metastasis group (24 specimens). RESULTS: Both MVD and VEGF expression were markedly increased in NPC tissue as compared with those in benign tumors of nasopharyngeal region. Both MVD and VEGF expression in NPC tissue with metastasis were statistically significantly increased as compared with those in NPC without metastasis. Therefore, the invasion and metastasis of NPC cells were closely related to MVD and the expression of VEGF in NPC tissue. CONCLUSION: The metastatic potency of NPC tissue and the prognosis of the patients with NPC can be estimated by measuring MVD and the expression of VEGF in NPC tissue. Drugs that have inhibitory actions on angiogenesis could be useful to prevent metastasis of NPC cells in the patients.     

Prognostic value of Survivin and Livin in nasopharyngeal carcinoma

BACKGROUND AND OBJECTIVES: Survivin and Livin are new members from the family of anti-apoptotic factors. Increased levels of Survivin and Livin have been observed in many malignancies and correlated with poor prognosis. Survivin is expressed almost exclusively in proliferating cells, including various kinds of cancers, but Livin expression is relatively rare in cancer cells. Therefore, the present study examines the expressions of Survivin and Livin in nasopharyngeal carcinoma (NPC) and investigates whether their expression contributes to the prognosis of NPC. METHODS: We investigated the expression of Survivin and Livin in 80 NPC samples using immunohistochemistry stain and correlated it with the survival of these patients using log-rank test and Cox multifactor regression analysis. RESULTS: All the patients were followed up at least for 60 months. During the following period, 21 cases developed distant metastasis, 9 cases developed local-regional recurrence, and 5 developed both distant metastasis and local-regional recurrence. Among them, 30 patients died of recurrence of tumor. In addition, the expression of Survivin was related with distant metastasis. Patients with low Survivin expression had better overall survival, disease-free survival and distant metastasis-free survival rates than the group with high Survivin expression (P = .0086, .0097, and .0318, respectively). Cox regression analysis confirmed that high Survivin expression was related to worse prognosis in NPC patients. However Livin expression level was not related with the survival of patients with NPC. CONCLUSION: NPC expresses high levels of Survivin and Livin, which may play an important role in the oncogenesis and tumor development. Over-expression of Survivin was related with poor prognosis. We suggest that the determination of Survivin expression may provide predictive information on NPC patients.     

Association of vascular endothelial growth factor expression with angiogenesis and lymph node metastasis in nasopharyngeal carcinoma.

OBJECTIVE: Recent experimental evidence indicates that angiogenesis affects tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is considered to be an important regulator of tumor angiogenesis. The present study was designed to examine the role of VEGF on angiogenesis and lymph node metastasis in primary nasopharyngeal carcinomas (NPCs). STUDY DESIGN: Formalin-fixed paraffin-embedded biopsy specimens were obtained from 29 primary NPCs that consisted of 22 differentiated nonkeratinizing carcinomas and seven undifferentiated carcinomas. METHODS: Microvessels were highlighted by staining endothelial cells with von Willebrand factor (VWF) using immunohistochemical techniques, and were counted (per x 400 field) in the most active area of angiogenesis on light microscopy. The expression of VEGF was also studied with immunohistochemistry. Positive ratio for VEGF was graded on a scale of 1 and 2. Scale 1 represents patients with less than the mean value of the positive ratio, and scale 2 represents patients with more than the corresponding value. RESULTS: There was a significant correlation between increased microvessel count and the progression of regional lymph node involvement. The microvessel counts and the progression of N factor were significantly higher in scale 2 patients than in scale 1 patients. CONCLUSION: These results suggest that VEGF plays an important role in lymph node metastasis through induction of angiogenesis in NPCs.     

鼻咽癌雌孕激素受体表达与远处转移的相关性

目的：探索雌孕激素受体——雌激素受体（ER）和孕酮受体（PR）表达与鼻咽癌远处转移的相关性,为预后判断提供参考指标。方法：用免疫组织化学SP法检测81例鼻咽癌患者的组织标本。结果：①ER和PR在鼻咽癌组织中的阳性表达率分别为35．8％和53．1％;②PR在T分期中其表达强度有统计学意义（P〈0．01）,PR在Ⅳ。阳性表达率和表达强度均明显高于其他各期（均P〈0．01）;③ER和PR在远处转移患者（包括放疗前和放疗后）中的阳性表达率均明显高于放疗后无瘤生存5年以上患者（P〈0．01和P〈0．05）。结论：鼻咽癌组织中ER和PR阳性表达与远处转移呈正相关,阳性表达尤其强阳性者提示预后不良。内分泌治疗有可能减少或推迟远处转移的发生。     

鼻咽癌组织中转移抑制基因和血管内皮生长因子蛋白表达及其临床意义

目的 探讨转移抑制基因（non—metastatic gene-23-H1，nm23-H1）和血管内皮生长因子（vessel endothelium growth factor，VEGF）蛋白表达与鼻咽癌（nasopharyngeal carcinoma，NPC）预后的相关性。方法 对108例鼻咽癌放疗前活检标本进行检测，应用免疫组织化学技术检测nm23-H1和VEGF基因蛋白在鼻咽癌组织中的表达情况，并分析两基因的表达与鼻咽癌分期、放疗敏感性、生存率、转移及复发之间的关系。结果 鼻咽癌组织中nm23-H1和VEGF蛋白阳性表达率分别为48．1％和59．3％。单因素分析表明，鼻咽癌分期、淋巴转移、生存率及远处转移与nm23-H1蛋白低表达均有密切关系，而VEGF的高表达则与鼻咽癌的分期、淋巴转移、放疗敏感性、生存率及复发均有密切关系。nm23-H1蛋白表达与VEGF表达呈负相关（r=-0．577，P〈0．05）。结论 nm23-H1蛋白低表达和VEGF高表达对判断病变进展，预测放疗敏感性，生存率及转移和复发有重要参考价值。     

鼻咽癌放疗后颈部淋巴结残留或复发对预后的影响

目的探讨鼻咽癌放疗后颈部淋巴结残留或复发对预后的影响。方法对67例鼻咽癌放疗后颈部淋巴结残留或复发而原发灶未复发的患者的临床病理资料进行回顾分析。选择性别、年龄、原发癌病理类型、残留或复发淋巴结大小、累及的侧数、淋巴结累及区域、累及区域数量、复发淋巴结的手术方式、颈动脉是否受侵、术后是否有严重并发症、是否补充放疗、是否复发、有无远处转移等临床病理因素,用χ2检验和Cox回归进行单因素和多因素分析,并用Kaplan-Meier法对残留和复发患者进行生存分析。结果单因素分析显示有无远处转移与预后明显相关,多因素分析结果表明,残留或复发淋巴结大小、是否累及Ⅴ区、残留或复发淋巴结累及区域数量、手术方式和有无远处转移与预后明显相关。Kaplan-Meier法进行生存分析显示颈部淋巴结残留或复发患者再次治疗的总1、3、5年生存率分别为88.6%、52.2%、38.6%,而采用根治性手术较采用局部手术生存率高。结论远处转移是影响鼻咽癌放疗后颈部淋巴结残留或复发患者预后的决定性因素。而残留或复发淋巴结大小、是否累及Ⅴ区、累及区域数量和手术方式也是重要因素,根治性手术可提高生存率。     

The effect of FoxP3 on tumour stage,treatment response,recurrence and survivalability in nasopharynx cancer patients

Objectives: To investigate the relationship between the cell percentage of T regulator (Treg) cells of patients’ specimens and disease severity, survivability, recurrence and metastasis in patients who were diagnosed with nasopharyngeal carcinoma (NPC). Design, Setting and Participants: Sixty patients who were diagnosed as NPC and treated by the same protocol were enrolled to the study. Patient files were reviewed retrospectively and their clinical and pathological results were recorded. Deparaffinized samples of nasopharyngeal carcinoma patients were stained immunohistochemically with anti‐FoxP3 monoclonal antibody. All patients’s Anti‐FoxP3 stained slides were evaluated by the same pathologist. Stained Treg lymphocytes around the tumoral foci were investigated. Patients were divided into two groups according to the total anti‐FoxP3‐stained Treg cell counts of the specimens; that is, less than 20% of the total or more than 20% of the total. These groups were compared statistically. Main Outcome Measures: Intensity of FoxP3 which is related to negative tumor response was the main outcome measure. It was evaluated in terms of stage, survival, recurrence and metastasis. Results: The study group consisted of 42 male patients (70%) and 18 female patients (30%). The mean age was 47 ± 14.9. NPC subtypes among the patients were undifferentiated non‐keratinized type in 54 patients (90%), differentiated non‐keratinized type in 4 patients (6.66%) and keratinized type squamous cell carcinoma (SCC) in 2 patients (3.33%). When the two groups were compared in terms of pathological subtype, there was no significant variation between the two groups. There was also no significant variation between the two groups when compared on the basis of tumor stage (P = 0.36 for T phase, P = 0.122 for N phase), early stage, late phase (P = 0.15), survival rate (P = 0.69 for general survival), recurrence (P = 0.2 for local recurrence, P = 0.37 for regional recurrence) and distant metastasis (P = 0.3). Conclusion: There was no significant relationship between the concentration of these cells in the stained specimens and the disease stage, survival rate, recurrence and distant metastasis discovered.