Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications

Toi, Masakazu; Matsumoto, T; Bando, Hiroko

doi:10.1016/s1470-2045(01)00556-3

Cited by 235 publications

(138 citation statements)

References 33 publications

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“…Although we have not examined all the cases that we used in the current study by Western blot analysis, the measurement of sVEGFR-1 expression with appropriate lysis buffer is meaningful with this ELISA system. Total VEGF was determined to be a potent and independent prognostic indicator in both node-negative and node-positive cancers as reported in the previous studies (Toi et al, 2001;Ferrara et al, 2003). No significant prognostic value of free VEGF was observed in this study.…”

Section: Discussionsupporting

confidence: 63%

“…Numerous studies have indicated that intratumoral VEGF expression is significantly correlated with microvessel density and poor prognosis in a variety of human solid cancers including breast cancer, brain tumours, head and neck cancer and gastrointestinal cancer (Toi et al, 2001;Ferrara et al, 2003). The prognostic value of VEGF has been confirmed not only in immunohistochemical studies but also in other studies using enzyme-linked immunosorbent assay (ELISA) and Northern blotting.…”

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confidence: 93%

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Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

et al. 2005

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Vascular endothelial growth factor (VEGF) receptors consist of three cell-membrane type receptors (VEGFR-1, VEGFR-2 and VEGFR-3), and soluble form of VEGFR-1 (sVEGFR-1), an intrinsic negative counterpart of the VEGF. In this study, we measured intratumoral protein levels of free and total VEGF, VEGFR-2 and sVEGFR-1 from 202 primary breast cancer tissues and examined their prognostic values. A significant inverse correlation was found between free or total VEGF and oestrogen receptor (ER) status ( P =0.042 and 0.032, respectively). A univariate analysis showed that low sVEGFR-1 and high total VEGF were significantly associated with poor prognosis in disease-free survival (DFS) and overall survival (OS). The ratio of sVEGFR-1 to total VEGF was a strong prognostic indicator (DFS: P =0.008; OS: P =0.0002). A multivariate analysis confirmed the independent prognostic values of total VEGF and the ratio of sVEGFR-1 to total VEGF. In subgroup analysis, total VEGF was a significant prognostic indicator for ER-positive tumours but not for ER-negative tumours, whereas sVEGFR-1 was significant for ER-negative tumours but not for ER-positive tumours. In conclusion, the intratumoral sVEGFR-1 level, VEGF level and the ratio of sVEGFR-1 to total VEGF are potent prognostic indicators of primary breast cancer, and might be relevant to ER status.

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Section: Discussionsupporting

confidence: 63%

mentioning

confidence: 93%

Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

et al. 2005

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“…VEGF stimulates proliferation, migration and tube formation of endothelial cells in vitro and regulates vascular permeability in vivo (Veikkola and Alitalo, 1999). VEGF expression correlates with angiogenesis and prognosis in several tumours including breast, lung and malignant mesothelioma (Toi et al, 2001;Strizzi et al, 2001). Several polymorphisms have been described within the promoter and 5'UTR of the VEGF gene, some of which (+405 C4G, 71154G4A and -2578C4A) correlate with VEGF production.…”

Section: Vascular Endothelial Growth Factormentioning

confidence: 99%

Role of genetic polymorphisms in tumour angiogenesis

2002

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Angiogenesis plays a crucial role in the development, growth and spread of solid tumours. Pro-and anti-angiogenic factors are abnormally expressed in tumours, influencing tumour angiogenesis, growth and progression. Polymorphisms in genes encoding angiogenic factors or their receptors may alter protein expression and/or activity. This article reviews the literature to determine the possible role of angiogenesis-related polymorphisms in cancer. Further research studies in this potentially crucial area of tumour biology are proposed.

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“…4 The prognostic value of VEGF in breast cancer has been shown by immuno-histochemical analysis and ELISA in a number of studies. 5 Cytosolic VEGF concentrations in breast tumours have been shown to be associated with tumour size and predict both relapse-free and overall survival of node-negative breast cancer patients. 6 The VEGF gene contains eight exons and seven introns over a 14-kb region 7 and has been mapped to chromosome 6p12 by fluorescence in situ hybridization.…”

mentioning

confidence: 99%

Influence of VEGF‐A gene variation and protein levels in breast cancer susceptibility and severity

Balasubramanian

Cox

Cross

et al. 2007

Intl Journal of Cancer

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Vascular endothelial growth factor‐A (VEGF‐A) plays an important role in tumour angiogenesis and cancer progression. VEGF gene variation may influence VEGF levels and therefore cancer susceptibility and progression. We studied the role of VEGF single nucleotide polymorphisms and haplotypes in breast cancer susceptibility and severity. We also studied the relationships of VEGF SNPs with circulating VEGF levels in healthy volunteers and protein expression in breast cancers. Single nucleotide polymorphisms (SNPs) in the regulatory regions of the VEGF gene were genotyped by high throughput methods in ∼500 breast cancer cases and 500 appropriate controls. Haplotype frequencies were inferred using methods based on the Expectation Maximisation algorithm. The effect of VEGF genotypes on serum and plasma VEGF levels were studied in another cohort of healthy individuals. A semi‐quantitative assessment of VEGF protein expression on tissue micro arrays (TMA) constructed from ∼300 breast cancer samples was performed and compared with VEGF genotypes and with histopathological parameters and survival in breast cancer. The −460T/+405C/−7C/936C haplotype in the VEGF gene was found to be associated with decreased breast cancer risk (p = 0.029). The −7C>T polymorphism may influence overall breast cancer survival (p = 0.027). Individual polymorphisms however did not affect breast cancer susceptibility. There was no association between the individual polymorphisms and circulating VEGF levels in healthy volunteers and VEGF expression on the breast cancer micro array. VEGF expression in breast cancers was however associated with high grade (p = 0.002) and ER negative tumours (p = 0.03). © 2007 Wiley‐Liss, Inc.

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Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications

Cited by 235 publications

References 33 publications

Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

Role of genetic polymorphisms in tumour angiogenesis

Influence of VEGF‐A gene variation and protein levels in breast cancer susceptibility and severity

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