Expression of platelet-derived endothelial cell growth factor and vascular endothelial growth factor in hepatocellular carcinoma and portal vein tumor thrombus

Purpose: Both platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) are known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. We aimed at evaluating the gene expression of PD-ECGF and VEGF in hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). Patients and methods: Surgical specimens (28 HCC, 28 nontumorous liver tissues and 18 PVTT) were studied by Northern blot analysis. The levels of PD-ECGF mRNA and VEGF mRNA expression were measured by densitometric scanning of the autoradiographs, and they were normalized to the level of expression of an internal control (glyceraldehyde-phosphate dehydrogenase) mRNA. Results: The expression rates of PD-ECGF mRNA in PVTT, HCC and nontumorous liver tissues were 77.8% (14/18), 67.9% (19/28) and 35.7% (10/28), being 88.9% (16/18), 75.0% (21/28) and 17.9% (5/28) respectively for VEGF mRNA. The expressions of PD-ECGF mRNA and VEGF mRNA were higher in HCC with PVTT than when PVTT was absent (P < 0.05). The PVTT was more often seen in patients with positive expression of both PD-ECGF mRNA and VEGF mRNA in HCC than in patients who were positive for only one of these factors or negative for both (P < 0.05). Conclusion: Both PD-ECGF and VEGF correlated well with the formation of PVTT of HCC. Received: 20 June 1999 / Accepted: 20 July 1999     

Serum vascular endothelial growth factor: a prognostic factor in cervical cancer

Purpose  To study pre-treatment serum VEGF of patients with invasive cervical cancer and its possible role as prognostic indicator. Methods  VEGF was measured using ELISA in the largest patient group (n = 167) to date. Reults  Serum VEGF was significantly higher in advanced tumor stage (P = 0.01), large tumor size (tumors larger than 2 cm) (P = 0.03), and the presence of vascular space invasion (P = 0.05). Serum VEGF was associated with disease free and overall survival [DFS: Hazard Ratio (HR) = 2.61; 95% CI 1.32–5.17; P = 0.006; for OS: HR = 2.09; 95% CI 1.54–2.84; P < 0.001, respectively]. In multivariate Cox regression serum VEGF retained its prognostic value for DFS (HR = 2.10, P = 0.03) and OS (HR = 1.92, P = 0.04). Conclusions  Serum VEGF levels correlate with more advanced and more aggressive disease in cervical cancer and may be a useful prognostic factor in patients with cervical cancer.     

Expression of vascular endothelial growth factor in surgical specimens of hepatocellular carcinoma

Purpose: Vascular endothelial growth factor (VEGF) has been reported to play an important role in angiogenesis in hepatocellular carcinoma (HCC). However, there is great variation in reports on the distribution of VEGF expression, especially in non-carcinoma liver cells. Furthermore, some reports have mentioned that endothelial cells were positive for VEGF antibody but have not evaluated its significance. In this study, we focused our attention to these problems and try to solve them. We also analyzed the factors influencing VEGF expression and evaluated the prognostic potential of VEGF protein in HCC. Methods: We examined the VEGF expression in specimens surgically removed from 46 HCC patients and 3 patients with liver cancer metastatic from the colon, and in 4 specimens of liver tissue with benign disease, by immunohistochemical methods. Results/conclusions: VEGF was expressed in HCC cells and hepatocytes and on vascular endothelial cells. Our finding that about seven times more endothelial cells were positive for VEGF antibody in carcinoma areas than in non-carcinoma areas (P < 0.001) suggests that VEGF is a very important angiogenesis factor for HCC growth. VEGF expression in HCC cells and non-carcinoma liver cells and on endothelial cells did not closely correlate with the disease recurrence rate (P > 0.05), suggesting that VEGF expression may not be useful as an individual factor for estimating the prognosis of HCC. A statistical analysis of the relationships between VEGF expression and clinicopathological variables revealed the following: preoperative transcatheter arterial embolization enhanced VEGF expression in both HCC cells and non-carcinoma liver cells. The histological grade of HCC and the level of alanine aminotransferase was related to VEGF expression in non-carcinoma liver cells and on endothelial cells in HCC areas. Tumor size and the histological status of the accompanying chronic hepatitis also influenced the VEGF expression on endothelial cells. Our findings concerning not only HCC but also the surrounding liver and endothelial cells may provide useful information for further research on the role of VEGF expression in HCC patients. Received: 29 July 1999 / Accepted: 11 October 1999     

血管内皮生长因子与血小板衍化内皮细胞生长因子在老年人胃癌组织中的表达

目的　探讨老年人胃癌术前活检标本血管内皮生长因子 (VEGF)和血小板衍化内皮细胞生长因子 (PD ECGF)的表达及其与老年胃癌患者预后的关系。　方法　采用免疫组化法检测 92例老年胃癌VEGF、PD ECGF表达情况 ,并分析它们与胃癌临床病理特征关系及对预后的影响。　结果　VEGF、PD ECGF在胃癌组织的表达明显高于慢性萎缩性胃炎 ,进展期癌的表达又高于早期癌(P <0 0 1) ,VEGF、PD ECGF表达呈显著正相关 (相关系数R =0 4 0 5 4 )。VEGF、PD ECGF的阳性表达随着肿瘤大小、浸润深度、TNM分期的递增而呈上调表达 ,有淋巴结转移、血管癌栓的患者表达也明显高于无淋巴结转移、血管癌栓者 (P <0 0 1)。VEGF、PD ECGF阳性表达者总体生存率明显低于VEGF、PD ECGF阴性表达者 (P <0 0 1) ,VEGF、PD ECGF共同表达者生存率更低 (P <0 0 1)。多因素分析表明 ,淋巴结转移、TNM分期、VEGF的表达是老年人胃癌独立的预后因素。　结论　VEGF与PD ECGF表达呈正相关 ,均与胃癌生长、浸润转移关系密切 ,可作为估计老年人胃癌预后的重要因素。     

Vascular endothelial growth factor expression in pN2 non-small cell lung cancer: lack of prognostic value

OBJECTIVE: Although several previous studies have investigated the prognostic significance of vascular endothelial growth factor (VEGF) expression in non-small cell lung (NSCL) cancer, no previous study has concentrated on NSCL cancer with pathologically abnormal mediastinal nodes (pN2). METHODOLOGY: A total of 60 patients with pN2 NSCL cancer who had undergone a complete resection with a systematic mediastinal lymph node dissection were reviewed retrospectively. Immunohistochemical examination, using antibodies against VEGF, was conducted. The prognostic significance of VEGF expression and clinicopathological factors were analysed. RESULTS: The overall 5-year survival rate was 21.7%. With respect to clinicopathological factors, single N2 involvement and skip metastasis were significantly associated with patients' survival. Expression of VEGF was found in 35/60 (58.3%) patients. VEGF expression was not related to the clinicopathological parameters examined. There was no relationship between survival rates and patients positive and negative for VEGF. Multivariate analysis showed that single N2 disease was an independent prognostic factor, while VEGF expression was not. CONCLUSIONS: Although VEGF expression might be important for tumour development and maintenance, no prognostic significance of VEGF expression in pN2 NSCL cancer was found.     

Correlation between synovial blood flow signals and serum vascular endothelial growth factor levels in patients with refractory rheumatoid arthritis

The objective of the study is to examine the relationship between synovial blood flow signals and vascular endothelial growth factor (VEGF) involved in angiogenesis by Doppler ultrasound. Twenty-one patients meeting the diagnostic criteria of the American College of Rheumatology (ACR) were enrolled in this study. Doppler ultrasound signals of blood flow in the wrist synovial membrane were measured and classified into three grades: grade 1 = no flow; grade 2 = mild flow; grade 3 = intense flow. A significant correlation was observed between blood flow signals in the wrist synovial membrane and serum VEGF levels (r = 0.5681, P = 0.0072). These results suggest that the measurement of Doppler ultrasound signals of blood flow in the wrist synovial membrane is useful in the evaluation of angiogenesis.     

血管内皮生长因子表达与肺癌预后的相关性研究

目的　研究血管内皮生长因子（ 以下简称 Ｖ Ｅ Ｇ Ｆ） 表达与肺癌的预后相关性。方法　应用 Ｓ Ｐ 免疫组化方法研究 Ｖ Ｅ Ｇ Ｆ 在６０ 例肺癌患者组织中的表达。结果　 Ｖ Ｅ Ｇ Ｆ 阳性表达率为６０ ％ , Ｖ Ｅ Ｇ Ｆ阳性表达主要出现在肺癌组织中癌细胞胞浆内, Ｖ Ｅ Ｇ Ｆ 表达与肺癌的淋巴结转移、复发有关：其中 Ｎ１ 、 Ｎ２（ ＋ ） 组 Ｖ Ｅ Ｇ Ｆ 阳性率分别为５３ ％ 、８０ ％ ,高于 Ｎ０ 组（２３ ％ , Ｐ＜ ００１） , Ｖ Ｅ Ｇ Ｆ 阳性表达率在肺癌复发组（８０ ％ ） 高于无复发组（５３ ％ , Ｐ＜ ００５） ;３ 、５ 年生存率 Ｖ Ｅ Ｇ Ｆ（ ＋ ） 与 Ｖ Ｅ Ｇ Ｆ（ － ） 组分别为３１ ％ 、１１ ％ 和８８ ％ 、５０ ％ ;术后生存时间 Ｖ Ｅ Ｇ Ｆ 表达（ ＋ ） 组远低于 Ｖ Ｅ Ｇ Ｆ 表达（ － ） 组（ 分别为３１ ±７ 月,６４ ±７月, Ｐ＜ ００５） 。结论　 Ｖ Ｅ Ｇ Ｆ是促进肺癌组织血管生成的关键因素,是预测肺癌患者预后的重要指标。     

Tumor-infiltrating macrophages can predict favorable prognosis in hepatocellular carcinoma after resection

Purpose  To evaluate the prognostic value of tumor-associated macrophages (TAM), individually or synergistically with CD45RO + memory T cells (T_M), in hepatocellular carcinoma (HCC) patients following resection. Methods  The infiltration of TAM and T_M was assessed by immunohistochemistry in tissue microarray containing 302 HCC specimens. Correlations between TAM/T_M infiltration and clinicopathologic features, disease-free survival (DFS) and overall survival (OS) were statistically analyzed. Results  High TAM infiltration was associated with both improved DFS (P = 0.0021) and OS (P = 0.0481). Multivariate analysis identified TAM infiltration as independent prognostic factor for DFS (P = 0.004) and OS (P = 0.049). A second analysis clarified the synergistic effect of TAM&T_M infiltration for DFS (P = 0.004) and OS (P = 0.040). Conclusions  Both TAM infiltration alone and concomitant infiltration of TAM&T_M are associated with improved DFS/OS, suggesting that TAM could protect HCC patients from recurrence/metastasis and prolong survival by distinct mechanisms. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. This is an original work by all the authors and no previous presentations, reports, or publications contain any material that appears in the article. Yi-Wei Li and Shuang-Jian Qiu contributed equally to this work.     

EphA2, vascular endothelial growth factor,and vascular endothelial growth factor correlate with adverse outcomes and poor survival in patients with glioma

Purpose:To assess expression levels of Ephrin type-A receptor 2 (EphA2), vascular endothelial growth factor (VEGF), and von Willebrand factor (vWF), and assess their potentials as prognostic biomarkers to predict the risk of poor survival in patients with primary lower grade glioma.Method:The study included75 patients with histopathologically confirmed primary glioma (World Health Organization Grade IV). All patients underwent combined surgery and postoperative radiotherapy for the management of primary glioma. Immuno-histochemical analysis was performed to evaluate expression levels ofEphA2 and VEGF. Evaluation of tumor microvessel density was also performed at angiogenesis hot spots due to tumor growth. Main outcomes of the study were the prognostic efficiencies of EphA2, VEGF, and vWF in primary low-grade glioma, as well as whether their expression levels were associated with cancer progression.Results:Of the patients with glioma, 67% had very strong expression of EphA2. Overall survival was inversely correlated with the expression of EphA2. Regarding VEGF expression, 38 patients (51%) had strong expression, 29 patients (39%) had weak expression, and 8 patients (11%) had no expression. Strong VEGF expression was associated with poor prognosis and poor survival.Conclusion:EphA2, VEGF, and vWF could be considered prognostic markers for assessment of primary glioma.     

Antecedent hypoglycaemia attenuates vascular endothelial growth factor response to subsequent hypoglycaemia in healthy men

Aim The plasma concentration of vascular endothelial growth factor (VEGF) has recently been shown to increase sharply in response to hypoglycaemia and, thus, has been proposed as having a role in hypoglycaemia counter‐regulation. Many counter‐regulatory hormones show a reduced response after antecedent hypoglycaemia. We therefore investigated whether this decrease in responsiveness with repetitive hypoglycaemia also pertains to VEGF. Methods Three hypoglycaemic clamp experiments were performed on two consecutive days in 15 healthy men. VEGF response was assessed during the first and last hypoglycaemic period. Results As expected, plasma VEGF concentrations rose markedly during the clamps (P < 0.001). The increase was distinctly blunted during the third (+13 ± 8 pg/ml) as compared with the first (+54 ± 18 pg/ml) hypoglycaemic clamp (P = 0.046). Conclusion This data confirms that circulating VEGF concentrations increase acutely during hypoglycaemia. Like the counter‐regulatory hormones, the hypoglycaemia‐induced rise in VEGF is attenuated after antecedent hypoglycaemia. The origin of increased systemic VEGF concentration during hypoglycaemia and its physiological role remains to be defined.     

Levels of vascular endothelial growth factor and hepatocyte growth factor in sera of patients with rheumatic diseases

Abstract

Angiogenesis plays an important role in the progression of rheumatic disease. We measured the levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in sera from patients with rheumatic diseases and investigated whether these angiogenic factors would be useful in the evaluation of rheumatic diseases. Serum VEGF and HGF levels were determined using ELISA in 128 patients with rheumatic diseases and in 11 healthy controls. Serum VEGF and HGF levels were significantly higher in patients with rheumatic diseases compared to healthy controls [VEGF, 312 ± 20?pg/ml versus 61 ± 8?pg/ml (mean ± SE), P < 0.001; HGF, 935 ± 36?pg/ml versus 413 ± 49?pg/ml, P < 0.01]. Serum VEGF and HGF levels were significantly elevated in patients with adult Still's disease (VEGF, 1021 ± 258?pg/ml; HGF, 1500 ± 295?pg/ml) and were relatively increased in patients with active rheumatoid arthritis (RA) (VEGF, 359 ± 94?pg/ml) and systemic sclerosis (SSc) (VEGF, 356 ± 43?pg/ml; HGF, 1294 ± 224?pg/ml). HGF levels correlated with the clinical course and disease severity in rheumatic disease patients. VEGF levels correlated with the presence of Raynaud's phenomenon (P < 0.05), interstitial lung disease (ILD) (P < 0.05), and serum KL-6 levels (P < 0.01), whereas HGF levels correlated with cryoglobulinemia (P < 0.05), ILD (P < 0.05), serum C-reactive protein (CRP) (P < 0.05), thrombomodulin (P < 0.05), and KL-6 levels (P < 0.05) in rheumatic disease patients. VEGF levels correlated with the skin scores and KL-6 levels in SSc patients and also correlated with the disease activity of RA patients. These data suggest that serum VEGF and HGF levels are related to rheumatic disease activity and the presence of complications. Analysis of VEGF and HGF may be useful in the clinical evaluation of rheumatic disease patients.     

Endocan Expression Correlated with Poor Survival in Human Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in China. We aimed to first present the expression of endocan in HCC tissue and its correlation with the clinicopathological features and overall survival of patients with HCC after curative hepatectomy. Immunohistochemical detection of endocan, CD34, and vascular endothelial growth factor (VEGF) were performed on samples from 100 patients with HCC. Endocan protein was expressed in endothelium of HCC tissue in all specimens, but was not expressed in endothelium of pericarcinomatous liver tissue and normal liver tissue. Microvessel density (MVD) denoted by endocan (endocan-MVD) in HCC was correlated with microscopic venous invasion and VEGF expression (P < 0.05). Survival analysis showed that overall survival of patients was inversely associated with endocan-MVD (P < 0.01). Multivariate analysis showed that endocan-MVD was an independent prognostic marker for overall survival of HCC (P < 0.01). In conclusion, endocan-MVD was a significant factor to predict the prognosis of HCC patients after curative hepatectomy.     

Expression of platelet-derived endothelial cell growth factor in inflammatory bowel disease

Background: Platelet-derived endothelial cell growth factor (PD-ECGF) is reported to be highly expressed in tumors and inflammatory tissues, but its expression and role in inflammatory bowel disease (IBD) are still unclear. In this study we examined the location and tissue density of cells immunoreactive for PD-ECGF in the colonic mucosa of IBD. Methods: Paraffin-embedded sections of colonic tissue from patients with ulcerative colitis (UC) or Crohn's disease (CD) were immunostained for PD-ECGF. As controls, noninflamed mucosa of IBD, as well as normal colonic mucosa from patients with colorectal cancer, were used. Also, cancer tissues were evaluated. In addition, changes in the expression of PD-ECGF in human umbilical vein endothelial cells (HUVEC) after treatment with inflammatory cytokines and angiogenic factors, as well as after coculture with colon cancer cell lines, were evaluated by flow cytometry. Results: In normal colonic mucosa and noninflamed mucosa of IBD, PD-ECGF expression was negligible. In inflamed colonic mucosa, strong expression was observed, predominantly in macrophages and fibroblasts. Vascular endothelial cells of the inflamed colonic mucosa, but not of normal colonic mucosa or of neoplastic tissues, stained for PD-ECGF, and the microvessel density was significantly increased in the severely inflamed mucosa. Flow cytometry demonstrated that PD-ECGF was constitutively expressed in HUVEC. Inflammatory cytokines and vascular endothelial growth factor (VEGF) increased its expression, whereas basic fibroblast growth factor (bFGF) decreased it. Coculture with colon cancer cell lines in direct contact, but not in those without contact, also resulted in an important decrease in the expression of PD-ECGF in HUVEC. Conclusions: Autocrine production of PD-ECGF by endothelial cells may be a mechanism of inflammatory angiogenesis, but not tumor angiogenesis, and may be particularly important for the maintenance of damaged vasculature in IBD. Received: September 17, 2001 / Accepted: September 6, 2002 Acknowledgments. This study was supported partly by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and partly by a grant from the Ministry of Health, Labour, and Welfare of Japan. Reprint requests to: S. Saito, Present address: Department of Surgery, Chigasaki Municipal Hospital, 5-15-1 Honson, Chigasaki 253-0042, Japan     

Levels of vascular endothelial growth factor and hepatocyte growth factor in sera of patients with rheumatic diseases

 Angiogenesis plays an important role in the progression of rheumatic disease. We measured the levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in sera from patients with rheumatic diseases and investigated whether these angiogenic factors would be useful in the evaluation of rheumatic diseases. Serum VEGF and HGF levels were determined using ELISA in 128 patients with rheumatic diseases and in 11 healthy controls. Serum VEGF and HGF levels were significantly higher in patients with rheumatic diseases compared to healthy controls [VEGF, 312 ± 20 pg/ml versus 61 ± 8 pg/ml (mean ± SE), P < 0.001; HGF, 935 ± 36 pg/ml versus 413 ± 49 pg/ml, P < 0.01]. Serum VEGF and HGF levels were significantly elevated in patients with adult Still's disease (VEGF, 1021 ± 258 pg/ml; HGF, 1500 ± 295 pg/ml) and were relatively increased in patients with active rheumatoid arthritis (RA) (VEGF, 359 ± 94 pg/ml) and systemic sclerosis (SSc) (VEGF, 356 ± 43 pg/ml; HGF, 1294 ± 224 pg/ml). HGF levels correlated with the clinical course and disease severity in rheumatic disease patients. VEGF levels correlated with the presence of Raynaud's phenomenon (P < 0.05), interstitial lung disease (ILD) (P < 0.05), and serum KL-6 levels (P < 0.01), whereas HGF levels correlated with cryoglobulinemia (P < 0.05), ILD (P < 0.05), serum C-reactive protein (CRP) (P < 0.05), thrombomodulin (P < 0.05), and KL-6 levels (P < 0.05) in rheumatic disease patients. VEGF levels correlated with the skin scores and KL-6 levels in SSc patients and also correlated with the disease activity of RA patients. These data suggest that serum VEGF and HGF levels are related to rheumatic disease activity and the presence of complications. Analysis of VEGF and HGF may be useful in the clinical evaluation of rheumatic disease patients. Received: February 19, 2002 / Accepted: August 13, 2002 Acknowledgment We are grateful to Ms. Aki Nomura for assistance with the ELISA of VEGF and HGF.     

Angiogenesis and cathepsin expression are prognostic factors in pancreatic adenocarcinoma after curative resection

Summary Background. Curative resection of pancreatic adenocarcinoma is the only clinical parameter related to a favorable prognosis while other clinicopathological parameters fail. To evaluate whether angiogenesis, vascular endothelial growth factor (VEGF) or certain tumor proteases, e.g., cathepsin B (CTSB) and L (CTSL), are factors of prognostic relevance, we investigated their expression in patients with long- and short-term survival after curative resection (R0) because of pancreatic adenocarcinoma. Methods. Twenty-nine tissue samples from patients with adenocarcinoma of the pancreas were examined. The patients were selected in a long-term survival group with a survival ≥24 mo (n=18) and a short-term survival group of patients, who died within 8 mo after surgery because of their malignancy (n=11). The microvessel quantification was performed immunohistochemically using a monoclonal anti-CD34 antibody. VEGF, CTSB, and CTSL expressions was studied using polyclonal antibodies (PAbs). Results. The median microvessel density (MVD) was 75 (range 39–182). MVD correlated significantly with the survival time after surgery (p=0.0132) but not with clinicopathological parameters. In cancer cells, VEGF was positive in 82.8% and showed significant correlation with the MVD (p=0.0002) and survival time (p=0.0395). Positive immunoreactivity could be obtained for 96.5% for CTSB and 84.2% for CTSL. Expression of both proteases correlated significantly with the survival time after surgery (CTSB p=0.0002, CTSL p=0.0001). Furthermore, CTSB expression correlated with invasion of the perineural space. Thus, a short postoperative survival correlated with a high MVD, and highly expressed VEGF, CTSB, and CTSL. No significant correlation between MVD, VEGF, as well as CTSL and clinicopathological parameters was found. For routinely assessed markers (e.g., TNM-stage, UICC-stage, and so on) no significant correlation with survival time was found in this small group of patients. Conclusion. These findings indicate that the MVD, VEGF, CTSB, and CTSL are prognostic factors after curative resection, whereas other parameters (TNM, UICC, and so on) failed to show prognostic relevance in our group of patients. Furthermore, the correlation between MVD and VEGF underlines the importance of this growth factor for angiogenesis and tumor growth. The correlation between CTSB and perineural invasion demonstrates the involvement of cathepsins in local tumor invasion.     

Protein expression profiling of vascular endothelial growth factor and its receptors identifies subclasses of hepatocellular carcinoma and predicts survival

Purpose  To examine expression profile and prognostic significance of vascular endothelial growth factor (VEGF) and its receptors in hepatocellular carcinoma (HCC) and peritumoral tissue. Methods  Expression of VEGF-A, VEGF-C, and VEGF receptor 1(VEGFR-1), VEGFR-2, and VEGFR-3 in tumor and peritumoral liver tissue was studied by immunohistochemistry in a tissue microarray from 107 patients with HCC. Unsupervised hierarchical cluster analyses were conducted to identify relevant clusters. Results  Staining of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 was mostly found on the tumor cells and peritumoral hepatocytes, but VEGFR-1 was mostly expressed in stromal cells. In most of the cases, the expression of VEGF-A, VEGFR-1, VEGFR-2, and VEGFR-3 in was higher in peritumoral liver tissue, while VEGF-C expression was higher in tumor. Unsupervised hierarchical clustering analysis identified four prognostically different clusters, of which cluster A was classified into the “poor prognosis group,” and the other three clusters were classified into the “good prognosis group” (P = 0.047). Further analysis with a set of seven markers reproduced the same four cluster groups with significantly different recurrence free probability (RFP) (P = 0.018), and the low RFP group was associated with more intrahepatic satellite lesions. Multivariate analysis showed that classification defined by seven biomarkers was of prognostic significance (P = 0.000). Conclusions  Expression of VEGF and its receptors was higher in peritumoral tissue than in tumor in HCC. Seven biomarkers predicted patients’ RFP, which consisted of tumoral expression of VEGF-A, VEGFR-1, and VEGF-C as well as peritumoral expression of VEGF-A, VEGFR-1, VEGFR-2, and VEGFR-3. J.-B. Jia and P.-Y. Zhuang contributed equally to this work.     

Simultaneous elevation of the serum concentrations of vascular endothelial growth factor and interleukin-6 as independent predictors of prognosis in aggressive non-Hodgkin's lymphoma

Therapeutic approaches for non-Hodgkin's lymphoma (NHL) are currently based on the International Prognostic Index (IPI). Research on biological prognostic factors has been actively pursued in recent years, with serum vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) being identified as prognostic factors for NHL. Here, we determined that serum VEGF and IL-6 levels are independent prognostic factors for aggressive lymphoma. Compared with normal controls, serum VEGF and IL-6 levels were significantly higher in patients with aggressive lymphoma or adult T-cell leukemia/lymphoma. Furthermore, overall and disease-free survival rates for patients with high levels of VEGF or IL-6 were significantly poorer than for patients with low levels. In addition, the prognosis for patients with high levels of both serum VEGF and IL-6 was significantly poorer than that for patients with high levels of either VEGF or IL-6 or with low levels of both VEGF and IL-6. Multivariate analyses of a variety of prognostic factors, including the five IPI factors, revealed that serum VEGF and IL-6 were both independent prognostic factors for overall survival of aggressive lymphoma. Therefore, a combination of VEGF and IL-6 represents a useful prognostic factor for aggressive lymphoma.     

Determination of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas and the role of overexpression in leiomyosarcoma

Purpose To evaluate the prevalence and role of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcoma (STS).Patients and methods VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). The expression of VEGF was assessed according to the percentage of immunoreactive cells: more than 10% of the cells staining were graded as positive. No detectable staining or <10% (of cells) staining was graded as negative.Results Two hundred and seventy-three patients (164 females and 109 males) with a mean age of 56 years (range: 1–93 years) were included in the study. Sixty-eight of the 273 (24.91%) patients diagnosed with STS between 1986 and 2001 revealed VEGF overexpression. VEGF overexpression was predominantly seen in 30% (15/50) of patients with malignant fibrous histiocytoma (MFH), 20.45% (9/44) of dermatofibrosarcomas (DFS), 25% (9/36) of leiomyosarcomas (LMS), and 30% (6/20) of patients with carcinosarcomas (CS). Despite overexpression being seen in about a quarter of patients with STS, VEGF overexpression was of prognostic value in only those patients with the LMS histologic type, as VEGF overexpression was associated with a shorter survival in this subgroup(P=0.01, by log-rank sum test).Conclusion Twenty-four point nine per centof STS overexpress VEGF and interestingly there is diversity seen in VEGF expression amongst the various histologic subtypes of STS. LMS, CS, and MFH are more likely to reveal overexpression of VEGF than the other histologic subtypes. There was no relationship between survival and VEGF status in any subtype of STS, except LMS. There is an urgent need for larger studies to validate our findings. In addition, randomized clinical trials evaluating the efficacy of angiogenesis inhibitors in soft tissue sarcomas, especially LMS, are warranted.