Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma.

Maeda, Kiyoshi; Nishiguchi, Yukio; Yashiro, Masakazu; Yamada, Shinobu; Onoda, Naoyoshi; Sawada, Tetsuji; Kang, Soon-Myoung; Hirakawa, Kosei

doi:10.3892/ijmm.5.4.373

Cited by 36 publications

(39 citation statements)

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“…27). Thrombospondin expression did not correlate with pathologic features of the primary colorectal tumor, as shown by other researchers (4,5,28,29).…”

Section: Discussionsupporting

confidence: 58%

“…However, expression of TSP-1 has been associated with increased disease-free survival rates: 84% 5-year survival in primary colorectal tumors expressing TSP-1 compared with 55% in TSP-1-negative tumors in one study (4) and 91% survival versus 44% in TSP-1-negative tumors in another study (5). Studies in breast cancer have described reduced TSP-1 levels in association with more aggressive tumors (3).…”

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confidence: 99%

“…In colorectal cancer, TSP-1 has been shown to have both an antiangiogenic effect (4,5) and conversely be associated with venous invasion and tumor progression (6). However, expression of TSP-1 has been associated with increased disease-free survival rates: 84% 5-year survival in primary colorectal tumors expressing TSP-1 compared with 55% in TSP-1-negative tumors in one study (4) and 91% survival versus 44% in TSP-1-negative tumors in another study (5).…”

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confidence: 99%

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Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Sutton¹,

O’Byrne²,

Goddard³

et al. 2005

Clinical Cancer Research

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Purpose: The aim of this study was to examine the expression and prognostic relevance of thrombospondin-1 (TSP-1) in tumor biopsies taken from a consecutive series of liver resections done at the University Hospitals of Leicester and the Royal Liverpool Hospital. Experimental Design: Patients having undergone a liver resection for colorectal liver metastases at our institutions between 1993 and 1999 inclusive were eligible. Inclusion criteria were curative intent, sufficient tumor biopsy, and patient follow-up data. One hundred eighty-two patients were considered in this study. Standard immunohistochemical techniques were used to study the expression of TSP-1 in 5-Am tumor sections from paraffin-embedded tissue blocks. TSP-1 was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. Results: One hundred eighty-two patients (male, n = 122 and female, n = 60) ages between 25 and 81 years (mean, 61 years) were included. TSP-1 was expressed around blood vessels (n = 45, 25%) or in the stroma (n = 59, 33%). No expression was detected in the remaining tumors. TSP-1 significantly correlated with poor survival on univariate (P = 0.01 for perivascular expression and P = 0.03 for stromal expression) and multivariate analysis (P = 0.01 for perivascular expression). Conclusion: TSP-1 is a negatively prognostic factor for survival in resected colorectal liver metastases.Thrombospondin-1 (TSP-1) is a multidomain glycoprotein that modulates platelet aggregation, wound healing, protease activity, and cellular functions such as adhesion, motility, and growth (1). However, the precise function of TSP-1 in the growth of tumors is not straightforward. Evidence suggests that different fragments of the large TSP-1 molecule may individually facilitate different and opposing tumor-modulating properties, such as proangiogenic and antiangiogenic activity (2) and promotion/inhibition of tumor cell migration (3).In colorectal cancer, TSP-1 has been shown to have both an antiangiogenic effect (4, 5) and conversely be associated with venous invasion and tumor progression (6). However, expression of TSP-1 has been associated with increased disease-free survival rates: 84% 5-year survival in primary colorectal tumors expressing TSP-1 compared with 55% in TSP-1-negative tumors in one study (4) and 91% survival versus 44% in TSP-1-negative tumors in another study (5). Studies in breast cancer have described reduced TSP-1 levels in association with more aggressive tumors (3). It is noteworthy that these figures pertain to studies carried out in primary tumors. The aim of this study was to examine the expression and prognostic relevance of TSP-1 in resected colorectal liver metastases.

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“…27). Thrombospondin expression did not correlate with pathologic features of the primary colorectal tumor, as shown by other researchers (4,5,28,29).…”

Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Sutton¹,

O’Byrne²,

Goddard³

et al. 2005

Clinical Cancer Research

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“…For each trial, this RR was estimated by a method depending on the data provided in the publication. The simplest method consisted in the direct collection of RR, hazard ratio, or odds ratio, and their 95% confidence interval (CI) from the original article Tanigawa et al, 1997;Ishigami et al, 1998;Vermeulen et al, 1999;Maeda et al, 2000;White et al, 2002;Kaio et al, 2003b;Zheng et al, 2003;Galizia et al, 2004;Liang et al, 2004;Tamura et al, 2004). If not available, we looked at the total numbers of events and the numbers of patients at risk in each group to determine the RR estimate.…”

Section: Methodsmentioning

confidence: 99%

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

et al. 2006

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We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n ¼ 957) for RFS and 18 for OS (n ¼ 2383) and for VEGF in 17 studies, including nine studies for RFS (n ¼ 1064) and 10 for OS (n ¼ 1301). High MVD significantly predicted poor RFS (RR ¼ 2.32 95% CI: 1.39 -3.90; Po0.001) and OS (RR ¼ 1.44; 95% CI: 1.08 -1.92; P ¼ 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR ¼ 2.84; 95% CI: 1.95 -4.16) and OS (RR ¼ 1.65; 95% CI: 1.27 -2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.

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“…With regard to VEGF expression (Berney et al, 1998;Ishigami et al, 1998;Tokunaga et al, 1998;Cascinu et al, 2000;Lee et al, 2000;Maeda et al, 2000), no differences were observed between DFS and OS in patients with high or low VEGF-expressing tumours. It is also worthy of note that, differently from other studies (Amaya et al, 1997;Takahashi et al, 1997), we did not find any relation between MVD and VEGF expression.…”

Section: Molecular and Cellular Pathologymentioning

confidence: 99%

Role of biological markers in the clinical outcome of colon cancer

et al. 2002

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We investigated a number of biological markers, evaluated under strict intralaboratory quality control conditions, in terms of their role in predicting clinical outcome of patients with colon cancer treated with 5-FU-containing regimens. Colon cancer tissue from 263 patients enrolled onto two randomised clinical trials were studied for their cytofluorimetrically determined DNA content and their immunohistochemically evaluated microvessel density, vascular endothelial growth factor expression, thymidylate synthase expression and tumour lymphocyte infiltration. Disease-free survival and overall survival of patients were analysed as a function of the different variables. At a median follow up of 57 months, age, gender and Dukes' stage showed an impact on disease-free survival, whereas no biological marker emerged as an indicator of better or worse disease-free survival. Only histological grade and Dukes' stage were found to influence overall survival. The different biological variables, studied with particular attention for determination reliability, proved to have no impact on the clinical outcome of patients with colon cancer. Therefore, other markers must be identified to complement clinico-pathological variables in the management of this disease. British Journal of Cancer (2002) 87 , 868–875. doi: 10.1038/sj.bjc.6600569 www.bjcancer.com © 2002 Cancer Research UK

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Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma.

Cited by 36 publications

References 0 publications

Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

Role of biological markers in the clinical outcome of colon cancer

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