Prognostic Significance of Vascular Endothelial Growth Factor Protein Levels in Oral and Oropharyngeal Squamous Cell Carcinoma

Smith, Benjamin D.; Smith, Grace L.; Carter, Darryl; Sasaki, Clarence T.; Haffty, Bruce G.

doi:10.1200/jco.2000.18.10.2046

Cited by 235 publications

(162 citation statements)

References 35 publications

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“…VEGF was initially identified in 1983 as a protein secreted by tumor cells [15] . It is one of the most potent angiogenic factors expressed in various human cancers [16,17] . As an endothelial growth factor, VEGF stimulates endothelial cell proliferation, thus inducing the budding of new blood vessels around the growing tumor masses.…”

Section: Discussionmentioning

confidence: 99%

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Guo

Zhu

et al. 2012

Chin. J. Cancer Res.

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Objective: To investigate the expression level of serum vascular endothelial growth factor (VEGF) in patients with unresectable hepatocellular carcinoma (HCC) and its relationship with the clinicopathological characteristics, and to assess the impact of serum VEGF as a predictive factor for HCC prognosis during transarterial chemoembolization (TACE) treatments.Methods: Serum VEGF levels were measured using enzyme-linked immunosorbent assay (ELISA) in 60 random patients who underwent TACE or transarterial infusion (TAI) for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control. All patients' clinicopathological features were retrospectively analyzed. Serum VEGF levels were correlated with clinicopathological features of the HCC patients. The patients' survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test. The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis.Results: The median serum VEGF level in the HCC patients was 285 pg/ml (range 14−1,207 pg/ml), significantly higher than that of healthy controls (P=0.021). The serum VEGF levels were significantly correlated with platelet counts (r=0.396, P=0.002) but not other clinicopathological features. Patients with serum VEGF level >285 pg/ml had worse overall survival compared with those with serum VEGF level <285 pg/ml (P=0.002). By multivariate analysis, the serum VEGF level was a significant prognostic factor.Conclusion: High serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.

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Section: Discussionmentioning

confidence: 99%

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Guo

Zhu

et al. 2012

Chin. J. Cancer Res.

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“…For VEGF, a cutoff of 20% cytoplasmic staining in the tumor cells was used to distinguish low from high VEGF-expressing tumors, in order to be in consensus with the majority of the studies performed so far. [12][13][14] For Ki-67, nuclear staining was evaluated and a cutoff of 20% was used to separate tumors with low vs high mitotic rate, as described previously. 30,31 VEGF receptors are mainly expressed in tumor vasculature; 9 but their expression in cancer cells was also described.…”

Section: Antibody Expressionmentioning

confidence: 99%

“…9 Studies examining the association between VEGF immunohistochemical expression and patients' survival in head and neck cancer are more consensus than those examining microvessel density, pointing towards a correlation with poorer overall survival. [10][11][12][13][14][15][16] Also, many studies failed to show association of VEGF expression with higher microvessel density. 15,16 These aspects raise the possibility that VEGF, which is produced by neoplastic cells, might serve not only for vessel sprouting, but have other functions as well.…”

mentioning

confidence: 99%

Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

et al. 2005

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Vascular endothelial growth factor is a peptide with well-defined actions on the vasculature and fundamental role in tumor angiogenesis. Its action in vascular endothelium is exerted in a paracrine manner. The immunohistochemical expression of this protein by cancer cells in head and neck squamous cell carcinoma was correlated with increased tumor aggressiveness and poor survival in previous studies. In the past years, an increasing amount of studies demonstrated potential autocrine action of vascular endothelial growth factor in various neoplasms. However, the existence and the impact of such autocrine action in head and neck cancer have not been demonstrated yet. In this retrospective study, we evaluated the expression of vascular endothelial growth factor and its receptors in neoplastic cells, in a cohort of patients with head and neck squamous cell carcinoma, and compared this expression with tumor aggressiveness, clinicopathologic parameters and outcome. High expression of vascular endothelial growth factor was strongly correlated with high expression of vascular endothelial growth factor receptor-2 (but not vascular endothelial growth factor receptor-1) on the cancer cells (Po0.001). The co-overexpression of both the protein and vascular endothelial growth factor receptor-2 was associated with higher tumor proliferation rate (Po0.001). The above cooverexpression also correlated with worse survival (log rank Po0.05) in patients with oral-larynx squamous cell carcinoma. Our results suggest that an autocrine vascular endothelial growth factor loop, mediated via vascular endothelial growth factor receptor-2, probably exists in head and neck squamous cell carcinoma. These observations support the hypothesis that the use of vascular endothelial growth factor receptor-2 inhibitors as adjuvant antiangiogenic therapy might have beneficial effects for these patients, by disrupting both paracrine (endothelial-dependent) and autocrine actions of vascular endothelial growth factor.

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“…It is a major angiogenic factor that induces endothelial cell proliferation and increases permeability of the vascular endothelium [4]. Tissue expression of VEGF correlates well with tumour progression and has been shown to be of prognostic significance in many malignancies [5][6][7][8][9]. Serum VEGF level may be a surrogate marker of tumour VEGF expression in patients with osteosarcoma, as-similar to tissue expression-it has prognostic significance [10][11][12][13][14][15][16], with significant association between a high VEGF expression in the primary tumour and poor prognosis [17,18].…”

Section: Introductionmentioning

confidence: 99%

Role of vascular endothelial growth factor as a tumour marker in osteosarcoma: a prospective study

Rastogi

Kumar

Sankineani

et al. 2012

International Orthopaedics (SICOT)

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Prognostic Significance of Vascular Endothelial Growth Factor Protein Levels in Oral and Oropharyngeal Squamous Cell Carcinoma

Abstract: In this cohort, VEGF positivity was the most significant predictor of poor prognosis. VEGF status may prove to be an important prognostic factor in head and neck cancer.

Cited by 235 publications

References 35 publications

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

Role of vascular endothelial growth factor as a tumour marker in osteosarcoma: a prospective study

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