VEGF-C表达对结肠癌预后的影响

目的:探讨VEGF-C表达与结肠癌临床病理指标的关系,评估VEGF-C表达对结肠癌预后的影响。方法:用免疫组化SABC法检测44例原发结肠癌及结肠腺瘤和正常结肠各7例VEGF-C表达,分析VEGF-C表达与临床病理指标和预后的关系。结果:结肠癌VEGF-C阳性表达率为43.2%(19/44),结肠腺瘤和正常结肠表达均阴性。结肠癌VEGF-C表达与肿瘤分化程度(P=0.003)、淋巴结转移(P=0.002)、Dukes分期(P=0.001)相关。VEGF-C(+)病人的中位生存期明显短于VEGF-C(-)病人(P=0.0225)。远处转移(P=0.0004)、淋巴结转移(P=0.021)、VEGF-C(P=0.0469)可以作为结肠癌独立的预后因素。结论:VEGF-C表达在结肠癌淋巴结转移中起重要作用,对于判断结肠癌侵袭性和预后有重要参考价值。     

检测微淋巴管及其密度和血管内皮生长因子C对结直肠癌的临床意义

目的探讨检测微淋巴管、微淋巴管密度(LMVD)和血管内皮生长因子C(VEGF-C)的表达对结直肠癌的临床意义。方法应用5′-核苷酸酶(5′-Nase)组织化学、SABC免疫组织化学(免疫组化)和RT-PCR检测80例结直肠癌组织和癌旁组织及30例结直肠正常组织的微淋巴管、LMVD和VEGF-C的表达,并随访、记录患者的临床病理参数和生存资料,分析其相关性。结果(1)结直肠癌、癌旁、正常结直肠组织的微淋巴管均被染成棕黄褐色。结直肠癌组织微淋巴管管腔封闭或无腔,为无功能淋巴管；癌旁组织微淋巴管丰富,管腔大,为功能性淋巴管。(2)癌旁组织LMVD为9．76±2．85,明显高于结直肠正常组织的5．49±．43(t=8．220,P＜0．01)；也高于癌组织的2．13±0．96(t= 15．118,P＜0．001)。(3)结直肠癌VEGF-C蛋白表达阳性率(48．8%)和相对表达量(1．09±1．20)明显高于正常结直肠组织(0和0),与VEGF-C mRNA表达一致；且VEGF-C表达与LMVD相关。(4) LMVD、VEGF-C表达与结直肠癌患者的年龄、性别、肿瘤部位大小、大体组织学类型无关(均P＞0．05)；与Dukes分期(P＜0．0001、P=0．0234)、淋巴结转移(P＜0．0001、P=0．0059)和生存期(P＜0．0001、P＜0．0001)密切相关。LMVD还与分化程度(P=0．0168)和肝肺血行转移(P=0．0088)相关。结论结直肠癌癌旁微淋巴管为功能性淋巴管；癌旁的功能性微淋巴管和增高的LMVD及肿瘤VEGF-C表达,可作为结直肠癌淋巴管生成的形态学特征、分子表型和判断结直肠癌患者淋巴转移及预后的重要指标。     

胃癌血管内皮生长因子的表达与微血管密度的关系及其临床意义

目的探讨胃癌组织中血管内皮生长因子（VEGF）的表达和微血管密度（MVD）的关系,以及这两项指标与临床病理特征和预后之间的关系。方法观察分析116例胃癌组织中VEGF的表达和计算微血管密度(MVD),分析VEGF的表达与MVD间的关系及它们与临床病理因素和预后的关系。结果116例胃癌组织中,VEGF的阳性率为60.34%。VEGF阳性组中的MVD值明显高于VEGF阴性组（分别为26.16±8.50和19.22±8.20,P<0.01)。在淋巴结转移组中VEGF表达的阳性率明显高于无淋巴结转移组(P<0.05)。在肿瘤分期晚的病人中,其VEGF表达的阳性率也明显高于分期早的(P<0.05)。MVD与胃癌的淋巴结转移及腹腔内转移有关(P均<0.01),且随TNM分期而增加(P<0.01)。VEGF表达阴性组和低MVD组(MVD<23)的5年生存率均明显高于VEGF表达阳性组和高MVD组(MVD≥23)(均P<0.01)。多因素分析表明,MVD和VEGF的表达均是独立的预后因素。结论胃癌组织中VEGF的表达和MVD能反映胃癌的恶性程度,是判断预后和指导辅助治疗的有效指标。     

低位直肠癌VEGF-C及LYVE-1检测的意义

目的探讨血管内皮生长因子C(VEGF-C)和淋巴管内皮细胞透明质酸受体1(LYVE-1)在低位直肠癌组织中的表达及意义。方法应用免疫组化法检测92例低位直肠癌组织VEGF-C及LYVE-1的表达水平及其与临床病理因素的关系。结果(1)淋巴结转移组VEGF-C的阳性表达率为62.1%,无淋巴结转移组阳性表达率为37.9%。LYVE-1可计算微淋巴管密度(LMVD),其阳性产物表达主要集中于癌组织边缘和正常黏膜的交界处。直肠癌组织中VEGF-C表达阴性者,LMVD是(1.95±0.56)个/HP;而VEGF-C表达阳性者,LMVD是(4.98±1.76)个/HP,两者差异有统计学意义(P0.05)。VEGF-C表达阳性者LYVE-1的表达率是47.9%。(2)LMVD与直肠癌的分化程度,TNM分期,淋巴结转移及远处转移有关;这4个指标各分组间差异有统计学意义(P0.01或P0.05)。结论VEGF-C和LYVE-1在直肠癌转移淋巴结中均呈高表达,可能有协同效应,共同促进直肠癌的淋巴转移。淋巴管生成在直肠癌的发展中起着重要作用,LMVD可作为直肠癌进展程度的重要指标。     

原发性胆囊癌组织中血管生成活性检测的临床意义

目的探讨血管生成与原发性胆囊癌临床病理特征和预后的关系.方法对42例原发性胆囊癌手术切除的肿瘤标本行免疫组织化学染色(SABC法),观察肿瘤内微血管计数(MVC)和血管内皮生长因子(VEGF)的表达.结果胆囊组织中MVC平均值为(70.4±20.7)个,VEGF表达阳性率为69.0%.MVC在细胞学分级为Ⅰ、Ⅱ级组中平均值为(57.9±15.4)个,在Ⅲ、Ⅳ级组中平均值为(88.8±11.5)个,两组相比较差异有显著性意义(P＜0.001); 在Nevin Ⅰ、Ⅱ、Ⅲ期病例组MVC平均值为(45.0±17.0)个,Ⅳ、Ⅴ期组平均值为(77.2±16.0)个,两组相比较差异有显著性意义(P＜0.001).VEGF表达阳性率与肿瘤细胞分级及肿瘤分期呈等级相关,分化差、分期晚者VEGF表达显著增高.VEGF的表达与MVC值呈显著正相关,MVC值高者或VEGF表达阳性者,3年生存率明显降低.结论胆囊癌中VEGF的分泌增多可导致微血管数目增加,促进了病变进展和转移.血管生成可作为判断胆囊癌预后的一项有效指标.     

血管和淋巴管生成及淋巴转移的关系

目的探讨胃癌组织中血管表皮生长因子C(VEGF-C)表达与血管和淋巴管密度及肿瘤淋巴转移的关系. 方法采用免疫组化SP法检测68例胃癌组织中VEGF-C、CD-31及淋巴管内皮标记物VEGFR-3,计算VEGF-C表达的阳性率及肿瘤微血管和微淋巴管密度. 结果淋巴结阳性组中VEGF-C阳性率(70%)显著高于淋巴结阴性组(30%), P<0.05;与VEGF-C阴性组(24.4±2.1)比较,VEGF-C阳性组淋巴管密度(29.6±3.0)明显增高,P<0.05,而微血管密度在两组之间差异无显著意义,P>0.05;与淋巴结阴性组比较,在淋巴结转移阳性组淋巴管密度(31.6±2.1)、微血管密度(40.2±2.3)均有显著提高,P<0.05. 结论 VEGF-C主要通过调节胃癌组织微淋巴管的生成而影响胃癌淋巴结转移;微淋巴管密度与微血管密度均为胃癌淋巴结转移的重要影响因素.     

膀胱移行细胞癌中VEGF-C的表达与患者预后的关系

目的:探讨血管内皮生长因子C(VEGF-C)在膀胱移行细胞癌(BTCC)中的表达及与预后的关系.方法:采用免疫组化方法研究45例膀胱移行细胞癌中VEGF-C的蛋白水平的表达,并分析该45例患者的预后随访情况;评估VEGF-C表达与淋巴管浸润、淋巴结转移等临床病理资料和预后的相关性.结果:Kaplan-Meier 生存曲线和Logrank test生存率显示VEGF C高表达组生存率低于VEGF C低表达组(P＜o.05);COX回归多因素分析发现淋巴结转移是患者预后不良的危险因素(P＜0.05).结论:检测膀胱移行细胞癌VEGF C表达能够预示盆腔淋巴结是否转移;VEGF-C通过促进肿瘤淋巴道的浸润和转移影响疾病的进展,可能成为一项新的预后判断指标;其表达情况可以提示患者术后是否必要进行辅助治疗.     

结肠癌淋巴结转移与活体组织中血管内皮生长因子的关系

目的　探讨结肠癌活体组织中血管内皮生长因子 (VEGF)、p5 3蛋白和增殖细胞核抗原 (PCNA)表达与淋巴结转移的关系。方法　应用病理学诊断方法检查淋巴结有无癌细胞转移 ,结肠癌组织标本作VEGF、p5 3蛋白和PCNA免疫组织化学染色。 结果　VEGF阳性表达结肠癌患者淋巴结转移率为 61.90 % ( 13 /2 1) ,VEGF阴性结肠癌淋巴结转移率为 2 6.67% ( 12 /4 5 ) ,差异有非常显著性 ( χ2 =7.5 5 5 7,P <0 .0 1) ;而 p5 3及PCNA阳性表达结肠癌患者淋巴结转移和阴性表达结肠癌患者的淋巴结转移之间差异无显著性 (P >0 .0 5 )。结论　结肠癌组织中VEGF的表达可为结肠癌患者的淋巴结转移情况的判断及预后提供参考。     

TGF-β1和VEGF在结肠癌组织中的表达和临床意义

目的:研究转化生长因子β 1 (TGF-β1)与血管内皮生长因子(VEGF)在结肠癌组织中的表达、相互关系及临床意义.方法:采用免疫组织化学SP法检测65例结肠癌组织标本中 TGF-β 1、VEGF蛋白表达,RT-PCR检测其mRNA表达,并选择39例正常人结肠黏膜组织作为正常对照.结果:免疫组化法检测TGF-β 1、VEGF蛋白在结肠癌组织中的阳性率较正常对照组明显增高(P＜0.05),RT-PCR检测TGF-β1、VEGF mRNA表达量癌组织高于正常组织.免疫组化检测的TGF-β1和VEGF表达阳性率在T3～T4高于T1～T2;有淋巴结转移组高于无淋巴结转移组DukesC～D期表达阳性率高于DukesA～B期,差异均有统计学意义(P＜ 0.05);VEGF和TGF-β1之间存在较明显的相关性(P＜0.05).结论:TGF-β 1、VEGF在结肠癌组织中呈高表达,与浸漓深度、淋巴结转移、Dukes分期密切相关,两者也存在相关性,与肿瘤进展及预后相关,可作为结肠癌判断预后的参考指标.     

淋巴管内皮生长因子-C在膀胱移行细胞癌中的表达及其临床意义

目的 :探讨具有促进淋巴管内皮细胞增殖和毛细淋巴管增生的淋巴管内皮生长因子 C(VEGF C)在膀胱移行细胞癌 (BTCC)中的表达及其与肿瘤淋巴管浸润、淋巴结转移等临床病理因素的关系。方法 :采用免疫组织化学方法研究 4 5例BTCC中VEGF C的表达水平 ,观察评估VEGF C的阳性表达与淋巴管浸润、淋巴结转移等临床病理资料的相关性。结果 :4 5例中 ,VEGF C阳性 36例 ,VEGF C的阳性表达与肿瘤分级、分期、静脉或淋巴管浸润、淋巴结及前列腺侵犯明显相关 (P <0 .0 5 ) ;多因素分析显示VEGF C的表达是唯一影响盆腔淋巴结转移的独立因素 (P =0 .0 0 3)。结论 :VEGF C与BTCC淋巴管浸润和转移有显著相关性 ,检测BTCC中VEGF C的表达能够预示盆腔淋巴结是否转移。     

VEGF-C、VEGFR-3在NSCLC中的表达与淋巴转移

目的 探讨VEGF-C及VEGFR-3与NSCLC淋巴转移间的关系,为了解患者预后提供依据。方法 采用免疫组化法检测65例NSCLC中VEGF-C及VEGFR-3的表达,结合临床病理特征进行分析。结果 NSCLC中VEGF-C和VEGFR-3的阳性率明显高于正常肺组织(P0.05)。二者在Ⅲ期NSCLC中的表达率明显高于Ⅰ、Ⅱ期,且随病理分级的增高而显著增加(P0.05),在有淋巴结转移者明显高于无淋巴结转移者(P0.05)。结论 VEGF-C及VEGFR-3在NSCLC中高表达,与其临床分期、病理分级、病理类型和淋巴结转移均密切相关。     

直肠癌中血管内皮生长因子C和血小板衍生生长因子AA、BB的表达及其与淋巴管生成和淋巴结转移的关系

目的探讨血管内皮生长因子C（VEGF-C）、血小板衍生生长因子（PDGF）-AA、PDGF-BB在直肠癌组织中的表达情况及其与患者淋巴管生成和淋巴结转移之间的关系。 方法采用免疫组织化学SP法检测60例直肠癌组织（直肠癌组）和30例正常组织（对照组）中VEGF-C、PDGF-AA和PDGF-BB的表达。应用D2-40检测直肠癌中微淋巴管密度（LMVD）,并做相关统计分析。 结果VEGF-C、PDGF-AA和PDGF-BB在直肠癌组织中阳性表达率均显著高于对照组(VEGF-C：63.3% vs 3.3%,P<0.05;PDGF-AA：40.0% vs 13.3%,P<0.05;PDGF-BB：55.0% vs 6.7%,P<0.05)。VEGF-C和PDGF-BB在淋巴结阳性组的阳性表达率较淋巴结阴性组均显著升高（VEGF-C：86.4% vs 50.0%,P<0.01;PDGF-BB：77.3% vs 42.1%,P<0.05）,但PDGF-AA表达与淋巴结转移无关（54.5% vs 31.6%,P>0.05）。直肠癌中淋巴结阳性组的LMVD高于淋巴结阴性组[（13.11±2.01）/mm² vs (8.13±2.99）/mm²,P<0.05],VEGF-C、PDGF-AA和PDGF-BB阳性表达组的LMVD高于阴性表达组[VEGF-C：（12.06±2.20） /mm² vs（6.32 ±2.41） /mm²,P<0.05;PDGF-AA：（11.89± 2.46）/mm² vs （8.67±3.67）/mm²,P<0.05;PDGF-BB：（12.19±2.22） /mm² vs（7.33 ±3.02）/mm²,P<0.05]。直肠癌中VEGF-C、PDGF-AA、PDGF-BB三者的表达具有显著相关性（VEGF-C vs PDGF-AA：r_s=0.366,P<0.05;VEGF-C vs PDGF-BB：r_s=0.650,P<0.05;PDGF-AA vs PDGF-BB：r_s=0.320,P<0.05）。 结论淋巴管生成是直肠癌淋巴结转移的重要原因之一,VEGF-C、PDGF-AA和PDGF-BB均参与直肠癌淋巴管生成,进而促进淋巴结转移,且三者可能存在一定的协同作用。针对VEGF-C、PDGF-AA、PDGF-BB的联合用药可能更利于直肠癌淋巴结转移的防治。     

The role of the lymphatic system and its specific growth factor, vascular endothelial growth factor C, for lymphogenic metastasis in prostate cancer

OBJECTIVE: To compare prostate carcinoma, with and with no lymph node metastasis, to benign prostatic hyperplasia (BPH) tissue for lymphatic vessel density (LVD) and the expression of the lymph-endothelial specific growth factor, vascular endothelial growth factor C (VEGF-C), to determine their role in lymphogenic metastasis. PATIENTS, MATERIALS AND METHODS: Lymphatic vessels were stained using lymphatic vessel endothelial hyaluronan receptor 1 and assessed in standard areas. The expression of VEGF-C was assessed by the number of positive epithelial cells. The data were compared with the clinical staging. RESULTS: The lowest LVD was found in tumorous areas as opposed to periphery and nontumorous tissue (P = 0.007; P < 0.001). The highest LVD was in BPH tissue (P < 0.001). There was no correlation with clinical staging. There was more VEGF-C staining in pN1 than in pN0 and in BPH specimens (P = 0.002). CONCLUSION: LVD is not a prognostic variable for the process of lymphogenic metastasis in prostate cancer. VEGF-C is up-regulated in prostate cancer and its correlation with lymph node status suggests a role for the development of lymph node metastasis, e.g. via an increased permeability of lymphatic vessels.     

Vascular endothelial growth factor-C (VEGF-C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder

PURPOSE: It has been found that expression of vascular endothelial growth factor-C (VEGF-C) in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis. However, VEGF-C expression in bladder transitional cell carcinoma (TCC) has not yet been reported. To elucidate the role of VEGF-C in bladder TCC, we examined VEGF-C expression in bladder TCC and pelvic lymph node metastasis specimens obtained from patients who underwent radical cystectomy. METHODS: Eighty-seven patients who underwent radical cystectomy for clinically organ-confined TCC of the bladder were enrolled in the present study. No neoadjuvant treatments, except transurethral resection of the tumor, were given to these patients. The VEGF-C expressions of 87 bladder tumors and 20 pelvic lymph node metastasis specimens were examined immunohistochemically and the association between VEGF-C expression and clinicopathological factors, including angiogenesis as evaluated by microvessel density (MVD), was also examined. RESULTS: Vascular endothelial growth factor-C expression was found in the cytoplasm of tumor cells, but not in the normal transitional epithelium. Vascular endothelial growth factor-C expression was significantly associated with the pathological T stage (P = 0.0289), pelvic lymph node metastasis (P < 0.0001), lymphatic involvement (P = 0.0008), venous involvement (P = 0.0002) and high MVD (P = 0.0043). The multivariate analysis demonstrated that VEGF-C expression and high MVD in bladder TCC were independent risk factors influencing the pelvic lymph node metastasis. Moreover, the patients with VEGF-C-positive tumors had significantly poorer prognoses than those with the VEGF-C-negative tumors (P = 0.0087) in the univariate analysis. The multivariate analysis based on Cox proportional hazard model showed that the independent prognostic factors were patient age (P = 0.0132) and pelvic lymph node metastasis (P = 0.0333). CONCLUSION: The present study suggests that VEGF-C expression is an important predictive factor of pelvic lymph node metastasis in bladder cancer patients.     

COX-2和VEGF-C表达与NSCLC淋巴转移的关系

目的探讨环氧化酶-2(COX-2)和血管内皮生长因子-C(VEGF-C)表达与淋巴管形成和淋巴结转移之间的关系。方法用免疫组化链霉素抗生物素蛋白-过氧化物酶(SP)法检测65例非小细胞肺癌(NSCLC)及16例正常肺组织中COX-2、VEGF-C及其受体VEGFR-3的表达;以VEGFR-3作标记计数肿瘤LVD,并结合临床病理特征进行统计学分析。结果65例NSCLC中COX-2和VEGF-C表达阳性率分别为76.9%(50/65)、72.3%(47/65)。COX-2表达与淋巴结转移(r=0.489,P<0.01)、临床分期(r=0.354,P<0.05)、VEGF0C(r=0.640,P<0.01)和LVD(r=0.518,P<0.01)呈正相关,而与病理分化程度呈负相关(r=-0.427,P<0.01)。VEGF-C表达与淋巴结转移(r=0.453,P<0.01)、临床分期(r=0.442,P<0.01)和LVD(r=0.624,P<0.01)呈正相关,与病理分化程度也呈负相关(r=-0.525,P<0.01)。结论NSCLC中COX-2与VEGF-C均高表达,COX-2可能通过VEGF-C促进肿瘤淋巴管生成和淋巴结转移。研究COX-2和VEGF-C在肿瘤中的协同作用有助于揭示肿瘤侵袭和转移的机制。     

Expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 in human prostate cancer is associated with regional lymph node metastasis

BACKGROUND: Vascular endothelial growth factor C (VEGF-C) and its receptor, VEGFR-3, have been implicated as important factors in the formation of lymphatic vessels and recent evidence suggests that tumor lymphangiogenesis promotes lymphatic metastasis. METHODS: The expression of VEGF-C and VEGFR-3 was examined in 22 human prostate cancer specimens with immunohistochemistry. A semi-quantitative scoring system was used for evaluation of staining. RESULTS: Expression of VEGF-C was stronger in prostate cancer areas in comparison to adjacent benign glands. In addition, patients with lymph node metastases had a significantly higher expression of VEGF-C than patients without lymph node metastases. Interestingly, VEGFR-3 was expressed in malignant prostate epithelial cells and its expression was significantly higher in the lymph node positive group compared to the lymph node negative group. CONCLUSIONS: The results of the present study indicate that increased expression of VEGF-C and VEGFR-3 play a role in prostate cancer progression and in metastasis to regional lymph nodes.     

Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer

OBJECTIVE: The aim of this study was to investigate the prognostic relevance of lymphangiogenesis and lymphovascular invasion in a large cohort of breast cancer patients. INTRODUCTION: Invasion of tumor cells into blood and lymphatic vessels is one of the critical steps for metastasis. The presence or absence of lymph node metastasis is one of the main decision criteria for further therapy. One shortcoming of previous morphologic studies was the lack of specific markers that could exact discriminate between blood and lymphatic vessels. The aim of this study was to evaluate the prognostic relevance of lymphangiogenesis and lymphovascular invasion in breast cancer patients. METHODS: We investigated 374 tissue specimens of patients suffering from invasive breast cancer by immunostaining for the lymphatic endothelial specific marker podoplanin. Lymphangiogenesis, quantified by evaluating the lymphatic microvessels density (LMVD), and lymphovascular invasion (LVI) were correlated with various clinical parameters and prognostic relevance. RESULTS: LMVD correlated significantly with LVI (P = 0.001). LVI was associated significantly with a higher risk for developing lymph-node metastasis (P = 0.004). Calculating the prognostic relevance, LVI presented as an independent prognostic parameter for disease free as well as overall survival (P = 0.001, and P = 0.001, respectively). CONCLUSION: Our data provide evidence that the biologic system of lymphangiogenesis constitutes a potential new target for development of anti-breast cancer therapeutic concepts. Our results further suggest that young, premenopausal patients with low differentiated breast tumors and high LMVD and LVI would, in particular, benefit from lymphangiogenesis-associated therapeutic strategies.