肾癌组织中血管内皮生长因子C的表达及血管生成的研究

目的研究肾癌组织(RCC)中血管内皮生长因子C(VEGF-C)的表达及微血管密度(MVD),探讨VEGF-C及MVD与肾癌生物学特征的联系。方法应用免疫组化S-P法,对53例肾癌及6例正常肾组织中VEGF-C进行检测,同时应用八因子抗体对肾癌组织中微血管进行染色,结合Meta-Morph显微荧光图像分析系统测定并分析53例肾癌中微血管密度,及其与VEGF-C和肾癌的病理分期、临床分级之间的关系。结果VEGF-C在正常肾组织呈阴性表达,在肾癌组织中呈不同程度的阳性表达,且过表达率在不同病理分级、临床分期组间有显著性差异(P<0.05)。MVD值在肾癌组织中不同病理分级、临床分期组间有显著性差异(P<0.05)。结论VEGF-C和MVD在肾癌组织中表达与肿瘤病理分级及临床分期密切相关,在肾癌浸润转移过程中起重要作用。     

Expression of vascular endothelial growth factor receptors is closely related to the histological grade of hepatocellular carcinoma

Angiogenesis is important for tumor growth, and is regulated by angiogenetic factors such as vascular endothelial growth factor (VEGF). In the present study, we investigated whether or not expression of VEGF receptors (VEGFRs) is related to the proliferation of tumor cells in hepatocellular carcinoma (HCC). We simultaneously stained proliferation marker Ki-67 antigen and either VEGFR1 (Flt-1) or VEGFR2 (Flk-1) on paraffin-embedded tissue sections from 50 cases of surgically resected human HCC. Based on the staining pattern of VEGFRs, we classified the cases into 4 categories; receptor double-negative, Flt-1 single-positive, Flk-1 single-positive, receptor double-positive. Interestingly, the Ki-67 index was significantly lower in receptor double-negative cases in comparison to that in either Flt-1 single-positive or Flk-1 single-positive cases (P = 0.0491, P = 0.0196, respectively). Moreover, the index was also significantly lower in receptor double-positive cases in comparison to either Flt-1 single-positive or Flk-1 single-positive cases (P = 0.0026, P < 0.0001, respectively). We further investigated 35 cases showing a Ki67 index > 10% to determine the expression of VEGFRs on Ki-67 antigen-positive proliferating cells. Surprisingly, the histological grade of HCC and the expression pattern of VEGFRs showed a characteristic relation; the well-differentiated HCC cases were all distributed in the Flk-1-positive group (7/7), moderately differentiated HCC cases were distributed in either the Flt-1 or Flk-1 single-positive group (20/21), and poorly differentiated HCC cases were predominantly distributed in either the receptor double-negative or double-positive group (6/7). These findings suggest that the expression pattern of VEGFRs influences the histological differentiation of HCC.     

Expression of vascular endothelial growth factor in primary non-small cell lung carcinoma

TumorgrowthisdependentuponangiogenesisifitdevelopsfromminimalsizesuchasImm3toabiggersize.[]]Themechanismbywhichtumorsinduceangiogenesishavereceivedconsiderableattentioninrecentyears.Oneofthetumor-secretedangiogenesisfactors,vascularendothelialgrowthfactor(VEGF),appearstoplayanimportantroleintumorangiogenesis.["']VEGFexpressionhasbeendetectedinseveralhumantumors,includingglioblastoma,["']ovarian,[']breast,l']colorectal,[']kidney,[']bladderll()Iandgastriccarcinomas.lll]Blockingwithanti-VEG…     

非小细胞肺癌组织中VEGF-C和VEGFR-3的表达及其临床意义

背景与目的:血管内皮生长因子-C(vascularendothelialgrowthfactorC,VEGF-C)和VEGFR-3是促进恶性肿瘤淋巴管形成的重要因子,其表达与恶性肿瘤的淋巴结转移关系密切。本文旨在研究VEGF-C和VEGFR-3蛋白在非小细胞肺癌(non-smallcelllungcancer,NSCLC)组织中的表达及其临床意义。方法:应用免疫组化方法检测77例NSCLC组织中VEGF-C和VEGFR-3表达情况,分析其与肿瘤淋巴管密度(lymphaticvesseldensity,LVD)、肿瘤的大小、癌的组织类型、组织分化程度、淋巴结转移情况、临床复发和术后生存期的关系。结果:77例NSCLC组织中有45例(58%)VEGF-C阳性,32例(42%)VEGFR-3阳性。NSCLC组织中VEGF-C表达与肿瘤组织的分化程度有关(r=-0.32,P=0.018);VEGF-C及VEGFR-3表达与肿瘤的淋巴结转移、LVD、肿瘤大小及术后生存期有关。NSCLC组织中VEGF-C与VEGFR-3表达相关(r=0.23,P=0.045)。结论:VEGF-C和VEGFR-3表达与NSCLC的淋巴结转移、预后相关,它的高表达提示肺癌患者容易出现淋巴结转移和预后不良。     

Expression of inducible nitric oxide synthase is significantly correlated with expression of vascular endothelial growth factor and dendritic cell infiltration in patients with advanced gastric carcinoma

OBJECTIVE: Nitric oxide (NO) is a product of L-arginine to L-citrulline conversion by nitric oxide synthase (NOS). The inducible form of NOS (iNOS) is one of three classes of NOS and the strongest producer of NO. It has been reported that NO correlates with angiogenesis and immune responses in some types of cancer, however, the correlations between iNOS expression, angiogenesis, and immune responses are still unclear in gastric carcinoma. METHODS: iNOS expression was determined in 135 gastric cancer patients by immunohistochemical procedures and compared with the expression of vascular endothelial growth factor (VEGF), microvessel (MV) density, and dendritic cell (DC) infiltration to evaluate the effect of iNOS on angiogenesis and immune responses in gastric carcinoma. RESULTS: iNOS expression was detected in 106 (78.5%) of 135 cases. There was a close correlation between iNOS expression and VEGF expression, a correlation with MV density and an inverse correlation with DC infiltration. There was no correlation between iNOS and p53 expression. The prognoses of patients whose tumors expressed iNOS were significantly worse than those of patients whose tumors did not express iNOS. Multivariate analysis indicated iNOS expression was an independent prognostic factor. CONCLUSION: iNOS might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric carcinoma.     

胃癌患者血清中血管内皮生长因子的表达及其与胃癌分期和预后的关系

目的探讨胃癌患者血清中血管内皮生长因子(VEGF)的表达及其与临床病理分期和预后的相关性。方法应用酶联免疫吸附法(ELISA)检测165例胃癌患者和45例健康志愿者血清中VEGF表达水平,并分析VEGF水平与与临床病理分期和预后的关系。结果胃癌患者血清中VEGF表达水平明显高于健康志愿者(P<0.05),其中Ⅲ~Ⅳ期胃癌患者血清中VEGF水平明显高于Ⅰ~Ⅱ期胃癌患者(P<0.05),出现转移者VEGF水平明显高于未发生转移者。结论 VEGF水平不仅与胃癌临床分期相关,而且也与预后密切相关,检测血清中VEGF的表达水平具有重要的临床意义。     

Expression of hypoxia-inducible factor (HIF)-1alpha is associated with vascular endothelial growth factor expression and tumour angiogenesis in human oesophageal squamous cell carcinoma

The purpose of this study was to examine the relationship between hypoxia inducible factor (HIF)-1alpha expression, vascular endothelial growth factor (VEGF) expression, and tumour vascularity in squamous cell carcinoma of the oesophagus. Expression of HIF-1alpha and VEGF was examined in two oesophageal squamous cell carcinoma cell lines (TE2, TE3) and 82 archival surgical specimens of human oesophageal squamous cell carcinoma tissue. In both cell lines, the levels of HIF-1alpha protein and VEGF mRNA were increased under hypoxic conditions. Thirty-two of the 82 (39%) tumour specimens showed high levels of HIF-1alpha immunoreactivity in the nuclei and/or cytoplasm of cancer cells. HIF-1alpha expression correlated significantly with venous invasion, VEGF expression, and microvessel density. Among the 47 patients who did not receive pre-operative chemotherapy, the outcome of those with high HIF-1alpha-expressing tumours was significantly poorer than that of those with low HIF-1alpha-expressing tumours. These results suggest that HIF-1alpha and VEGF expression are important determinants of survival in squamous cell carcinoma of the oesophagus.     

Increased serum levels of vascular endothelial growth factor in patients with renal cell carcinoma.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. One such factor, vascular endothelial growth factor (VEGF), is considered to exert a potent angiogenic activity, as indicated by immunohistochemical and molecular evidence. In this study we investigated the serum VEGF level (s-VEGF) in patients with renal cell carcinoma (RCC). s-VEGF in peripheral blood samples was analyzed in 40 RCC patients and 40 patients without cancer (controls) using a sandwich enzyme-linked immunoassay. In 20 RCC patients, serum samples were obtained separately from the bilateral renal veins. s-VEGF was also measured before, 4 and 8 weeks after nephrectomy in 11 patients. There were significant differences in s-VEGF between the RCC patients and the controls (207.3+/-32.9 vs. 71.5+/-9.1 pg/ml, mean+/-SE) (P<0.005), between the tumor-bearing renal veins and the contralateral ones (P<0.01), between the pre- and post-nephrectomy situations (P<0.01) and among the various parameters of tumor status such as tumor extent (P<0.001) and existence of metastasis (P<0.001). s-VEGF significantly correlated with the tumor volume obtained by a three-dimensional measurement (r=0.802, P<0.0001). The sensitivity and specificity of s-VEGF at the cut-off level of 100 pg/ml, as determined by the receiver-operating-characteristics curve, were 80.0% and 72.5%, respectively. The results indicate that tumor tissue of RCC liberates VEGF into the systemic blood flow and that s-VEGF is a possible marker for RCC.     

Expression of vascular endothelial growth factor and prognosis of oral squamous cell carcinoma

The correlation between expression of vascular endothelial growth factor (VEGF) and prognosis for oral squamous cell carcinoma was investigated. Tissue samples of oral squamous cell carcinoma were obtained from 63 patients. Of these patients, 11 had stage I, 17 had stage II, 9 had stage III, and 26 had stage IV tumours. Immunohistochemical expression of VEGF was quantitatively determined by computer-assisted image analysis. The value of VEGF expression was significantly higher for the patients with poor prognosis than for those with good prognosis (P=0.0423). Regarding regional lymph node metastasis, VEGF showed no significant difference between metastasis positive and negative patients. Expression of VEGF may thus be a prognostic marker for oral squamous cell carcinoma.     

Vascular endothelial growth factor overexpression is correlated with von Hippel-Lindau tumor suppressor gene inactivation in patients with sporadic renal cell carcinoma

BACKGROUND: A high frequency of genetic alterations of the von Hippel-Lindau (VHL) gene and overexpression of the vascular endothelial growth factor (VEGF) gene have been observed independently in human sporadic renal cell carcinoma (RCCs), but to the authors' knowledge the association between the two has not been characterized in primary sporadic RCC. In the current study the authors report the simultaneous comparison of the biallelic inactivation status of the VHL gene and VEGF expression levels in patients with sporadic RCC. METHODS: DNA and RNA were extracted from 27 sporadic RCC samples. Mutation was analyzed by direct sequencing of the amplified VHL DNA and cDNA. Loss of heterozygosity (LOH) of the gene was analyzed at three polymorphic markers. The VEGF mRNA was measured using Northern blot analysis. RESULTS: Mutations of the VHL gene were found in 14 of 27 RCC samples (51.9%). LOH analysis by a VHL-intragenic polymorphic marker and 2 extragenic microsatellite markers, D3S1560 and D3S1317, showed that LOH occurred in 10 of 15 RCC samples (66.7%). Overexpression of VEGF mRNA was observed in 17 of 27 RCC cases (63.0%): 15 of the 18 RCC samples estimated to have at least 1 hit, but only 2 of the 6 RCC samples with 0-1 hit, and none of the 3 RCC samples in which the VHL gene was not inactivated. CONCLUSIONS: VEGF overexpression was found to be correlated with both monoallelic and biallelic VHL inactivation. Alteration of the VHL gene is believed to cause angiogenesis in RCC cases through the overexpression of VEGF.     

血管内皮生长因子与肾细胞癌

血管内皮生长因子(VEGF)在肾细胞癌组织中高表达,主要受VHL基因和组织缺氧调控,可作为判断肾细胞癌患者肿瘤进展和预后的标志物.近年来将抗VEGF靶向药物用于肾细胞癌治疗,取得良好的临床疗效.     

Vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in the blood serum, tumor and renal parenchyma of patients with renal cell carcinoma

Serum, tumor and renal parenchyma levels of VEGF and VEGFR2 were compared in patients with renal carcinoma (RC) with reference to basic clinicomorphological characteristics of the disease. VEGF and VEGFR2 were estimated in 37 RC patients and 57 healthy controls (serum levels only). VEGF and VEGFR2 were detected in all the samples. Their concentrations in the serum were the same in the patients and controls. The tumor tissue contained more VEGF than renal parenchyma. In unfavorable clinicomorphological features the tumor contained higher content of VEGF, higher VEGF/VEGFR2, lower VEGFR2. Thus, angiogenic factors studied closely correlate with clinicomorphological characteristics of renal carcinoma: primary tumor size, stage of the disease, tumor differentiation, tumor pseudocapsule invasion.     

Association of vascular endothelial growth factor polymorphisms with clinical outcome of renal cell carcinoma patients

We investigated the association of three single nucleotide polymorphisms (SNPs) in VEGF gene with the prognosis of renal cell carcinoma (RCC) and its association with clinical characteristics of RCC, such as tumor stages, metastasis, and tumor size. Polymerase chain reaction (PCR) restriction fragment length polymorphism analysis was used to genotype specimens for three polymorphisms (?2578C/A, ?1154G/A, and ?634G/C) in the VEGF gene. Hazard ratios (HRs) and their confidence intervals (CIs) were used to analyze the association of three SNPs in the VEGF gene with survival time using a multivariate Cox proportional hazards model. Frequencies of VEGF?2578AA genotype and A allele were significantly higher in patients with III–IV tumor stage or larger tumor size when compared with CC genotype. Moreover, frequencies of VEGF?634CC genotype and C allele were significantly higher in patients with tumor size >4 cm when compared with ?634GG genotype. By Cox proportional hazards model, patients carrying VEGF?2578AA genotype and A allele significantly increased the risk of death from RCC, with the adjusted HRs (95 % CI) of 2.23 (1.15–4.36) and 1.55 (1.11–2.17), respectively. Our study suggests that VEGF?2578C/A and VEGF?634G/C polymorphisms may have effects on the prognosis of RCC. This finding might help in clarifying the mechanisms of RCC development and progression.     

血管内皮生长因子在卵巢上皮性癌中的表达

目的 探讨血管内皮生长因子（ｖｅｓｃｕｌａｒ ｅｎｄｏｔｈｅｌｉａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ,ＶＥＧＦ）在血管生成及其在卵巢癌发展中的作用。方法 用免疫组织化学方法检测ＶＥＧＦ在７９例人卵巢上皮性癌组织中的表达,并标记肿瘤内血管,分析ＶＥＧＦ与瘤内微血管密度（ｍｉｃｒｏｖｅｓｓｅｌ ｄｅｎｓｉｔｙ,ＭＶＤ）及其与组织学分类、临床分期、腹水、淋巴结转移、预后的关系。结果 在７９例卵巢上皮性癌中５     

肺癌血管内皮生长因子的表达及其临床意义

目的探讨血管内皮生长因子(VEGF)在人肺癌组织中的表达及其与微血管密度(MVD)、肿瘤复发和转移以及患者预后的关系.方法应用免疫组化的方法检测42例肺癌组织中MVD和VEGF表达的情况.结果VEGF在肺癌组织中的阳性表达率为81.0%;VEGF阳性表达组的肺癌组织平均MVD为(45.68±9.23)/每高倍视野,而阴性表达组的MVD为(34.58±10.22)/每高倍视野,两组之间的差异具有显著性(P＜0.01);VEGF的表达水平与肿瘤复发和转移呈正相关(P＜0.01),与术后生存时间呈负相关(P＜0.05).结论VEGF能促进肺癌组织中微血管的形成,因而在肺癌的复发和转移中起重要作用;VEGF可作为判断肺癌患者临床预后的参考指标.     

Inhibition of renal cell carcinoma angiogenesis and growth by antisense oligonucleotides targeting vascular endothelial growth factor

Angiogenesis is critical for growth and metastatic spread of solid tumours. It is tightly controlled by specific regulatory factors. Vascular endothelial growth factor has been implicated as the key factor in tumour angiogenesis. In the present studies we evaluated the effects of blocking vascular endothelial growth factor production by antisense phosphorothioate oligodeoxynucleotides on the growth and angiogenic activity of a pre-clinical model of renal cell carcinoma (Caki-1). In vitro studies showed that treating Caki-1 cells with antisense phosphorothioate oligodeoxynucleotides directed against vascular endothelial growth factor mRNA led to a reduction in expressed vascular endothelial growth factor levels sufficient to impair the proliferation and migration of co-cultured endothelial cells. The observed effects were antisense sequence specific, dose dependent, and could be achieved at a low, non-toxic concentration of phosphorothioate oligodeoxynucleotides. When vascular endothelial growth factor antisense treated Caki-1 cells were injected into nude mice and evaluated for their angiogenic potential, the number of vessels initiated were approximately half that induced by untreated Caki-1 cells. To test the anti-tumour efficacy of vascular endothelial growth factor antisense, phosphorothioate oligodeoxynucleotides were administrated to nude mice bearing macroscopic Caki-1 xenografts. The results showed that the systemic administration of two doses of vascular endothelial growth factor antisense phosphorothioate oligodeoxynucleotides given 1 and 4 days after the tumours reached a size of approximately 200 mm(3) significantly increased the time for tumours to grow to 1000 mm(3).     

Expression of vascular endothelial growth factor in renal cell carcinoma and the relation to angiogenesis and p53 protein expression

BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF) seems to play an important role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF expression. We investigated the effect of VEGF expression on renal cell carcinoma (RCC) and the correlation between the expression of VEGF and tumor angiogenesis and p53 protein expression. METHODS: Sixty-two RCCs were examined by immunohistochemical studies with anti-VEGF, anti-p53, and anti-CD34 antibodies. RESULTS: Forty tumors (80.6%) were classified as VEGF positive, and 28 tumors (45.2%) were positive for p53 protein. The microvessel density was 75.3 +/- 33.5. A significant correlation was found between VEGF expression and both the nuclear grade (P < 0.05) and the TNM stage (P < 0.05). The tumors with VEGF expression had a significantly higher microvessel density than those without VEGF expression (P < 0.01). There was no statistically significant correlation between p53 protein and VEGF expression. No statistically significant differences in survival were found to be associated with microvessel density, VEGF expression or p53 protein expression. By using multivariate survival analyses, nuclear grade (P < 0.05) and TNM stage (P < 0.05) were the only independent prognostic factors. CONCLUSIONS: Our data do not show a direct regulation of VEGF expression by p53. We suggest that VEGF expression plays a role in the promotion of angiogenesis in RCC.     

Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma

BACKGROUND: Vascular endothelial growth factor C (VEGF-C) plays an important role in lymphangiogenesis and activates VEGF receptor 3 (VEGFR-3). By contrast, lymphatic spread is an important prognostic factor in patients with nonsmall cell lung carcinoma (NSCLC). The objective of the current study was to determine whether the expression of VEGF-C and VEGFR-3 correlates with clinicopathologic factors and prognosis in patients with primary NSCLC. METHODS: The authors conducted a retrospective review of 180 consecutive patients who underwent complete resection for NSCLC and who did not receive any chemotherapy or radiotherapy prior to surgery. Immunohistochemical staining for VEGF-C and VEGFR-3 was performed. The clinicopathologic implications of VEGF-C and VEGFR-3 expression were analyzed statistically. RESULTS: Of 180 patients with NSCLC, 137 patients (76.1%) were positive for VEGF-C, and 40 patients (22.2%) were positive for VEGFR-3. VEGF-C expression was observed frequently in patients with adenocarcinoma (P = 0.026). For VEGFR-3 expression, significant correlations were demonstrated with age (P = 0.02), gender (P = 0.008), and histologic differentiation in patients with squamous cell carcinoma (P = 0.03). Patients who had positive staining for VEGF-C showed significantly less favorable survival rates compared with patients who had negative staining for VEGF-C (P = 0.003). The survival rates of patients who had positive staining for VEGFR-3 also were significantly lower compared with patients who had negative staining for VEGFR-3 (P < 0.001). Patients who had positive staining for both VEGF-C and VEGFR-3 exhibited the most unfavorable prognoses. Univariate analysis revealed the following prognostic factors: gender (P = 0.03), tumor status (T1,T2 vs. T3; P < 0.01), lymph node status (negative vs. positive; P < 0.01), tumor size (< or = 35 mm vs. > 35 mm; P < 0.01), disease stage (Stage I vs. Stages II and III; P < 0.01), VEGF-C expression (negative vs. positive; P < 0.01), VEGFR-3 expression (negative vs. positive; P < 0.01) and combined VEGF-C and/or VEGFR-3 expression (both positive vs. VEGF-C or VEGFR-3 positive; P < 0.01). Multivariate analysis demonstrated that VEGFR-3 expression was the only independent negative prognostic factor (P < 0.01). CONCLUSIONS: VEGF-C and VEGFR-3 expression may be indicative of survival rates for patients with NSCLC.     

Combined analysis of vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression in gastric carcinoma

Solid tumours require neovascularization for growth and metastasis. Both vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are well-characterized inducers of angiogenesis. In this study we examined the expressions of these antigens and their relationship with microvessel density and also determined their prognostic significance. Ninety-five specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumours that were both VEGF⁺ and PD-ECGF⁺ than in tumours that were both VEGF⁻ and PD-ECGF⁻. According to prognosis, patients with VEGF⁺ tumours had a significantly worse prognosis than did those with VEGF⁻ tumours. Although there was no significant correlation between PD-ECGF expression and prognosis, patients with PD-ECGF⁺ tumours tended to have a shorter survival than did those with PD-ECGF⁻ tumours. Moreover, the frequency of hepatic recurrence was significantly higher in patients with tumours that were both VEGF-positive and PD-ECGF⁺ than in all other patients. Int. J. Cancer 74:545–550, 1997. © 1997 Wiley-Liss, Inc.     

Vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 are related closely to the prognosis of patients with ovarian carcinoma

BACKGROUND: The vascular endothelial growth factor (VEGF) family and VEGF receptors (VEGFR) play an essential role in the angiogenesis of both pathologic and nonpathologic conditions. However, the prognostic significance of VEGF and VEGFR expression in ovarian carcinoma is unclear. METHODS: The tissue expression levels of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 in 80 specimens of ovarian carcinoma were examined immnohistochemically. The results obtained were analyzed clinicopathologically. RESULTS: VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 were expressed both in tumor cells and in adjacent endothelial cells of blood and lymph vessels. The tissue expressions of VEGF-C and VEGFR-2 were correlated significantly with tumor extension, including peritoneal metastases outside the pelvic cavity (P = 0.0010 and P = 0.0008, respectively), lymph node metastases (P = 0.0030 and P = 0.0018, respectively), and positive ascitic cytology (P = 0.025 and P = 0.0016, respectively). Conversely, there was no significant correlation between VEGF-A and VEGFR-3 expression and clinicopathologic features of ovarian carcinoma. Logistic regression analysis revealed that the expressions of VEGF-C and VEGFR-2 also were independent risk factors for peritoneal and lymph node metastases. Survival curves determined by the Kaplan-Meier method and in univariate analysis demonstrated that high expression levels of VEGF-C and VEGFR-2 were associated with the 5-year survival rate. In multivariate analysis, high expression levels of VEGF-C and VEGFR-2 emerged as independent indicators for disease-specific survival. CONCLUSIONS: High tissue expression of VEGF-C and VEGFR-2 reflects the aggressiveness of the spread of tumor in ovarian carcinoma. Thus, both have predictive value for identifying high-risk patients who have a poor prognosis.